Keratoconic Corneas Research Articles

The extraction and application of antisymmetric characteristics of the cornea during air-puff perturbations

BackgroundA non-contact tonometer is used to measure intraocular pressure, and studies have primarily relied on apex displacements to assess corneal properties. However, previous studies have overlooked the asymmetric characteristics of lateral corneal perturbations, leading to a gap in understanding of the lateral mechanical properties and its application. MethodTo investigate these lateral perturbations, we designed an experiment to sequentially record the corneal profiles when two consecutive air-puffs were applied at the center of the same cornea within a short period. Moreover, we used modal decomposition to decompose anterior surface profiles into symmetric and antisymmetric modes to comprehensively analyze the asymmetric characteristics. To extract mechanical properties, we utilized high-pass frequency analysis (>250 Hz) to filter out noise and errors. ResultsSymmetric modes between the two consecutive air-puffs exhibited major similarities during vibration; however, antisymmetric modes exhibited minor differences in lateral perturbations of asymmetric vibration. The antisymmetric modes might be related to air-puff misalignment and mechanical properties. Through applying frequency analysis, the mechanical properties could be proven at high frequencies and misalignment shown at low frequencies. Furthermore, we compared the corneal vibration profiles of 259 healthy participants and 50 patients with keratoconus. Their properties showed that the antisymmetric modes of the keratoconus group exhibited a completely opposite direction of deformation compared to that in the healthy group. ConclusionsOur proposed algorithm not only extracts antisymmetric characteristics but also offers valuable insights into decompose misalignment and mechanical properties of healthy and keratoconus corneas, presenting a new perspective for corneal biomechanics.

Identification of Comparative Collagen Fibril Associated Changes in Normal and Keratoconus Corneas using Vibrational Optical Coherence Tomography and Machine Learning

Vibrational Optical Coherence Tomography (VOCT) is a non-invasive technique that uses infrared light and audible sound to characterize tissues noninvasively.

Comparison of polynomial and rational function cornea models for effective dimensionality reduction

This study aims to examine geometric models of the corneal surface that can be used to reduce in reasonable time the dimensionality of datasets of normal anterior corneas. Polynomial models (P) like Zernike polynomials (ZP) and spherical harmonic polynomials (SHP) were obvious candidates along with their rational function (R) counterparts, namely Zernike rational functions (ZR) and spherical harmonic rational functions (SHR, new model). Knowing that both SHP and ZR were more accurate than ZP for the modeling of normal and keratoconus corneas, it was expected that both spherical harmonic (SH) models (SHP and SHR) would be more accurate than their Zernike (Z) counterparts (ZP and ZR, respectively), and both rational (R) models (SHR and ZR) more accurate than their polynomial counterparts (SHP and ZP, respectively) for a low dimensional space (coefficient number J < 30). This was the case. The SH factor contributed more to accuracy than the R factor. Considering the corneal processing time as a function of J, P models were processed in quasi-linear time with a quasi-null slope and rational models in polynomial time. Z models were faster than SH models, and increasingly so in their R version. In sum, for corneal dimensionality reduction, SHR is the most accurate model, but its processing time is increasingly prohibitive unless the best coefficient combination is identified beforehand. ZP is the fastest model and is reasonably accurate with normal corneas for exploratory tasks. SHP is the best compromise between accuracy and speed.

Performance of Corvis ST Parameters Including Updated Stress-Strain Index in Differentiating Between Normal, Forme-Fruste, Subclinical, and Clinical Keratoconic Eyes

PurposeThis study seeks to evaluate the ability of the updated stress strain index (SSIv2) and other Corvis ST biomechanical parameters in distinguishing between keratoconus with different disease stages, and normal eyes. DesignDiagnostic accuracy analysis to distinguish disease stages. Methods1084 eyes were included and divided into groups of normal (199 eyes), forme fruste keratoconus (FFKC, 194 eyes), subclinical keratoconus (SKC, 113 eyes), mild clinical keratoconus (CKC-I, 175 eyes), moderate clinical keratoconus (CKC-II, 204 eyes) and severe clinical keratoconus (CKC-III, 199 eyes). Each eye was subjected to a Corvis ST examination to determine the central corneal thickness (CCT), biomechanically corrected intraocular pressure (bIOP), SSIv2 and other eight Corvis parameters including the SSIv1, SP-A1, A1T, ARTh, IIR, DAM, DARatio2 and CBI. The sensitivity and specificity of these parameters in diagnosing keratoconus were analyzed through receiver operating characteristic curves. ResultsBefore and after correction for CCT and bIOP, SSIv2 and ARTh were significantly higher, and IIR and CBI were significantly lower in the normal group than in the FFKC group, SKC group and the 3 CKC groups (all P<0.05). There were also significant correlations between the values of SSIv2, ARTh, IIR, CBI and the CKC severity (all P<0.05). AUC of SSIv2 was significantly higher than all other Corvis parameters in distinguishing normal eyes from FFKC, followed by IIR, ARTh and CBI. ConclusionCorvis ST's updated SSI demonstrated superior performance in differentiating between normal and keratoconic corneas, and between corneas with different keratoconus stages. Similar, but less pronounced, performance was demonstrated by the IIR, ARTh and CBI.

Role of Fibroblast Growth Factor Receptor 2 (FGFR2) in Corneal Stromal Thinning.

To determine the role of fibroblast growth factor receptor 2 (FGFR2)-mediated signaling in keratocytes during corneal development, a keratocyte-specific FGFR2-knockout (named FGFR2cKO) mouse model was generated, and its phenotypic characteristics were determined. A FGFR2cKO mouse model was generated by the following method: FGFR2 flox mice were crossed with the inducible keratocyte specific-Cre mice (Kera-rtTA/tet-O-Cre). Both male and female FGFR2cKO- and control mice (1 to 3-months-old) were analyzed for changes in corneal topography and pachymetry maps using the optical coherence tomography (OCT) method. The comparative TUNEL assay and immunohistochemical analyses were performed using corneas of FGFR2cKO and control mice to determine apoptotic cells, and expression of collagen-1 and fibronectin. Transmission electron microscopic analysis was conducted to determine collagen structures and their diameters in corneas of FGFR2cKO and control mice. OCT-analyses of corneas of FGFR2cKO mice (n = 24) showed localized central thinning and an increased corneal steepness compared to control mice (n = 23). FGFR2cKO mice further showed a decreased expression in collagen-1, decreased collagen diameters, acute corneal hydrops, an increased fibronectin expression, and an increased number of TUNEL-positive cells suggesting altered collagen structures and keratocytes' apoptosis in the corneas of FGFR2cKO mice compared to control mice. The FGFR2cKO mice showed several corneal phenotypes (as described above in the results) that are also exhibited by the human keratoconus corneas. The results suggested that the FGFR2cKO mouse model serves to elucidate not only the yet unknown role of FGFR2-mediated signaling in corneal physiology but also serves as a model to determine molecular mechanism of human keratoconus development.

A Comprehensive Wavefront Assessment of Keratoconus Using an Integrated Scheimpflug Corneal Tomographer/Hartmann-Shack Wavefront Aberrometer.

To characterize higher-order aberrations (HOAs) in different severities of keratoconus (KC) from the anterior and posterior corneal surfaces and whole eye using an integrated Scheimpflug corneal tomographer/Hartmann-Shack wavefront aberrometer. This study included eyes with clinical KC, topographic KC (no clinical signs), fellow eyes with very asymmetric ectasia with normal topography and no clinical signs (VAE-NT), and control eyes. Corneal and ocular wavefront aberrations were obtained using an integrated Scheimpflug tomographer/Hartmann-Shack wavefront aberrometer. The diagnostic capability of distinguishing VAE-NT from the control was also tested. This study included 68 eyes with clinical KC, 44 with topographic KC, 26 with VAE-NT, and 45 controls. Clinical KC had significantly greater total HOAs and coma from the anterior and posterior corneal surfaces and whole eye than the other groups ( P <0.05). Although topographic KC had significantly greater values in all wavefront parameters than the control ( P <0.05), ocular and corneal HOAs did not differ between the VAE-NT and control groups. The coma from the anterior cornea in topographic KC was significantly greater than that in VAE-NT ( P <0.05); the coma from the posterior cornea and whole eye did not differ. Total HOAs from the anterior corneal surface exhibited the highest area under the receiver operating characteristic curve value of 0.774 (sensitivity, 73%; specificity, 78%). A comprehensive wavefront assessment can be used to quantitatively evaluate corneal and ocular HOAs across various severity of KC. Total HOAs from the anterior corneal surface exhibited the potential ability in distinguishing VAE-NT from the control eyes.

Contributed Session II: Detecting subclinical keratoconus by mapping corneal biomechanics using wave-based optical coherence elastography.

The detection of subclinical keratoconus in human corneas remains a challenging task. It is hypothesized that the focal reduction in biomechanical properties of the cornea would be the primary initiating event of keratoconus before changes in topography and pachymetry are manifested. We propose to use an air-couple ultrasonic optical coherence elastography system to map the elasticity of the corneas of 15 patients with a clinical diagnosis of keratoconus (KC) in one eye, and subclinical keratoconus (SK) in the fellow eye. The fully non-contact system excites the corneal apex to produce Lamb wave propagation and measures wave speed and average corneal thickness along 16 semi-meridians. Measurements in 30 human healthy subjects (control group: CG, N = 60 corneas) defined a baseline of normal biomechanics in two biomarkers: Spatial Anisotropy of Wave Speed (SAWS < 0.207), and the Speed-Thickness Index (STI > 0). SAWS was significantly higher in KC (0.353, p < 0.001) and SK (0.249, p < 0.001) corneas when compared to the CG. Moreover, STI maps show abnormal elasticity in SK (STI = -1.22) and KC (STI = -0.375) compared to the CG. Our results show important biomechanical differences in SAWS and STI between normal, subclinical, and advanced stages of keratoconus, suggesting those as potential biomarkers to identify "at-risk" corneas before changes in topography and pachymetry become evident.

Localized Refractive Changes Induced by Symmetric and Progressive Asymmetric Intracorneal Ring Segments Assessed with a 3D Finite-Element Model.

To build a representative 3D finite element model (FEM) for intracorneal ring segment (ICRS) implantation and to investigate localized optical changes induced by different ICRS geometries, a hyperelastic shell FEM was developed to compare the effect of symmetric and progressive asymmetric ICRS designs in a generic healthy and asymmetric keratoconic (KC) cornea. The resulting deformed geometry was assessed in terms of average curvature via a biconic fit, sagittal curvature (K), and optical aberrations via Zernike polynomials. The sagittal curvature map showed a locally restricted flattening interior to the ring (Kmax -11 to -25 dpt) and, in the KC cornea, an additional local steepening on the opposite half of the cornea (Kmax up to +1.9 dpt). Considering the optical aberrations present in the model of the KC cornea, the progressive ICRS corrected vertical coma (-3.42 vs. -3.13 µm); horizontal coma (-0.67 vs. 0.36 µm); and defocus (2.90 vs. 2.75 µm), oblique trefoil (-0.54 vs. -0.08 µm), and oblique secondary astigmatism (0.48 vs. -0.09 µm) aberrations stronger than the symmetric ICRS. Customized ICRS designs inspired by the underlying KC phenotype have the potential to achieve more tailored refractive corrections, particularly in asymmetric keratoconus patterns.

Screening of sensitive in vivo characteristics for early keratoconus diagnosis: a multicenter study.

Purpose: To analyze and compare sensitive in vivo characteristics for screening early keratoconus. Methods: This multicenter, case-control study included 712 eyes, after matching for age and biomechanically corrected intraocular pressure, from three clinics in different cities. The keratoconus (n = 288), early keratoconus (n = 91), and normal cornea (n = 333) groups included eyes diagnosed with bilateral keratoconus, fellow eyes with relatively normal topography with unilateral keratoconus, and normal eyes before refractive surgery, respectively. After adjusting for central corneal thickness, differences in vivo characteristics were analyzed among the three groups. The in vivo characteristics were measured by Pentacam and Corvis ST. Fifty-four indices were evaluated to screen for a sensitive index for the detection of early keratoconus. Results: Significant differences were observed in 26 of the 36 corneal biomechanical indeces between the early keratoconus and normal corneas. The area under the receiver operating characteristic curve of tomographic and biomechanical index, Belin/Ambrósio deviation, and Da in differentiating keratoconus from normal cornea was 1.000. Among the top five indeces of the area under the receiver operating characteristic curve for detecting early keratoconus, the corneal biomechanical-related index accounted for 80% (4/5), including A1 dArc length, highest concavity radius, A2 time, and tomographic and biomechanical index, of which the area under the receiver operating characteristic curve of A1 dArc length was 0.901. Conclusion: A1 dArc length and several corneal biomechanical indices are highly sensitive for the detection of early keratoconus, even in the absence of topographic abnormalities. Ophthalmologists should focus on the clinical application of corneal biomechanics and combine corneal tomography for the timely and accurate detection of early keratoconus.

Corneal Stress Distribution Evolves from Thickness-Driven in Normal Corneas to Curvature-Driven with Progression in Keratoconus

To introduce the novel parameter of Corneal Contribution to Stress (CCS) and compare stress distribution patterns between keratoconus (KCN) and normal corneas. Prospective, observational, cross-sectional study. The study included 66 eyes of 40 subjects diagnosed with KCN and 155 left eyes from 155 normal control (NRL) subjects. Tomography was obtained to calculate the newly proposed CCS, defined according to the hoop stress formula without intraocular pressure, R/2t, where R is the radius of curvature and t is the thickness. CCS maps were calculated from pachymetry and tangential curvature maps. Custom software identified the 2-mm-diameter zones of greatest curvature (Cspot-max), thinnest pachymetry (Pach-min), greatest stress (CCSmax), and lowest stress (CCSmin). Stress difference (CCSdiff) was calculated as CCSmax - CCSmin. Distances between Cspot-max vs. Pach-min, vs. CCSmax, and vs. CCSmin, as well as between Pach-min vs. CCSmax and vs. CCSmin, were calculated. t tests were performed between cohorts, and paired t tests were performed within cohorts. Univariate linear regression analyses were performed between parameters and distances. The significance threshold was P < 0.05. Corneal stress parameters, corneal features of maximum curvature, minimum thickness, and distances between corneal stress parameters and corneal features. CCSmax was significantly closer to Pach-min (0.79 ± 0.92) and Cspot-max (2.04 ± 0.85) than CCSmin (3.17 ± 0.38, 2.73 ± 1.53, respectively) in NRL, P < 0.0001, whereas CCSmin was significantly closer to Cspot-max (1.35 ± 1.43) than CCSmax (2.52 ± 0.72) in KCN, P < 0.0001. Cspot-max (severity) was significantly related to CCSdiff in KCN (P < 0.0001; R2= 0.5882) with a weak relationship in NRL (P < 0.0080, R2= 0.0451). Cspot-max was significantly related to the distance from Pach-min to CCSmax (P < 0.0001; R2= 0.3737) without significance in NRL (P= 0.8011). Corneal stress is driven by thickness in NRL, with greatest stress at thinnest pachymetry and greatest curvature. However, maximum stress moves away from thinnest pachymetry with progression in KCN, and minimum stress is associated with maximum curvature. Severity in KCN is significantly related to greater difference between maximum and minimum stress, consistent with the biomechanical cycle of decompensation. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Epithelial Thickness Mapping in Keratoconic Corneas: Repeatability and Agreement Between CSO MS-39, Heidelberg Anterion, and Optovue Avanti OCT Devices.

To assess repeatability and agreement of corneal epithelial thickness mapping in eyes with keratoconus using three optical coherence tomography (OCT) devices featuring different technologies: spectral-domain (SD) OCT combined with Placido disk corneal topography (MS-39), swept-source OCT (Anterion), and SD-OCT (Avanti). Three consecutive measurements were acquired with the three devices in 60 eyes with keratoconus. The mean epithelial thickness was calculated in the central 2-mm zone and in 2- to 5-mm and 5- to 7-mm diameter rings. The repeatability was calculated using pooled within-subject standard deviation (Sw). The agreement was assessed by paired t tests and Bland-Altman plots. The repeatability (Sw) of the epithelial thickness for the central 2-mm zone was 0.91, 0.71, and 0.93 μm for the MS-39, Anterion, and Avanti, respectively. All thicknesses with the MS-39 were greater than those of the Anterion and Avanti, with mean differences of 4.11 ± 1.34 μm (P < .001) and 0.52 ± 1.30 μm (P = .003), respectively. The 95% limits of agreement were 1.484 to 6.736 μm for the MS-39 and Anterion, -3.068 to 2.028 μm for the Avanti and MS-39, and 1.258 to 5.922 μm for for the Avanti and Anterion. Epithelial thickness mapping results were most repeatable with the Anterion, followed by the MS-39 and Avanti. The MS-39 gave the thickest values, followed by the Avanti and Anterion. The differences were significant, making the devices not interchangeable for epithelial thickness mapping in eyes with keratoconus. [J Refract Surg. 2023;39(7):474-480.].

Meta-Analysis of Keratoconus Transcriptomic Data Revealed Altered RNA Editing Levels Impacting Keratin Genomic Clusters.

Keratoconus (KC) is an ocular disorder with a multifactorial origin. Transcriptomic analyses (RNA-seq) revealed deregulations of coding (mRNA) and non-coding RNAs (ncRNAs) in KC, suggesting that mRNA-ncRNA co-regulations can promote the onset of KC. The present study investigates the modulation of RNA editing mediated by the adenosine deaminase acting on dsRNA (ADAR) enzyme in KC. The level of ADAR-mediated RNA editing in KC and healthy corneas were determined by two indexes in two different sequencing datasets. REDIportal was used to localize known editing sites, whereas new putative sites were de novo identified in the most extended dataset only and their possible impact was evaluated. Western Blot analysis was used to measure the level of ADAR1 in the cornea from independent samples. KC was characterized by a statistically significant lower RNA-editing level compared to controls, resulting in a lower editing frequency, and less edited bases. The distribution of the editing sites along the human genome showed considerable differences between groups, particularly relevant in the chromosome 12 regions encoding for Keratin type II cluster. A total of 32 recoding sites were characterized, 17 representing novel sites. JUP, KRT17, KRT76, and KRT79 were edited with higher frequencies in KC than in controls, whereas BLCAP, COG3, KRT1, KRT75, and RRNAD1 were less edited. Both gene expression and protein levels of ADAR1 appeared not regulated between diseased and controls. Our findings demonstrated an altered RNA-editing in KC possibly linked to the peculiar cellular conditions. The functional implications should be further investigated.

The Biomechanical E-Staging: In Vivo Biomechanics in Keratoconus.

Belin's ABCD keratoconus classification system allows keratoconus staging based on the criteria of anterior (A) and posterior (B) corneal curvature, thinnest corneal thickness (C), and best spectacle-corrected visual acuity (D). These parameters also provide a progression assessment, but do not take corneal biomechanics into account. The analysis of corneal biomechanics by the Corvis ST (Oculus, Wetzlar, Germany) allows for separation of healthy and keratoconus corneas, based on the Corvis Biomechanical Index (CBI) and the Tomographic Biomechanical Index (TBI). As Corvis ST measurements are highly reliable and are independent of keratoconus severity, a biomechanical parameter was developed for keratoconus corneas based on the linear term of the CBI. This provides biomechanical keratoconus staging. The Corvis Biomechanical Factor (CBiF) is the basis for the introduction of the biomechanical E-staging, which augments the ABCD classification to the ABCDE classification, thus including the cornerstone of corneal biomechanics. This article highlights strengths and limitations of the ABCDE classification. "Unilateral keratoconus" supposedly turns out to be mostly a snapshot of a highly asymmetric keratectasia. Regular astigmatism is sometimes an important differential diagnosis to keratectasia and may be difficult to differentiate from it. Furthermore, the use of the biomechanical E-staging in daily practice for progression assessment of keratoconus and after its treatment by corneal cross-linking or implantation of intracorneal ring segments will be demonstrated and discussed.

Случаи отсутствия лечебного эффекта кросслинкинга при лечении кератоконуса

Purpose. Study of changes in morphometric parameters of cornea in keratoconus before and after corneal collagen crosslinking (CXL). Material and methods. 35 patients (35 eyes) with progressive keratoconus stages 1–3. The indexes of photokeratoscopy were studied in depth (topographer Pentacam (Oculus, Germany). CXL was performed according to the Dresden protocol. A corneal lenticule was used in 6 eyes. The analysis of the studied parameters was carried out initially and after 12 months. Results. By the end of the observation, in all patients, the average values of maximum keratometry (Kmax) decreased statistically significantly from 54.5 to 53.1 diopters, which indicated positive trend. Most indices of keratoconus according to topographer data (ISV, IVA, KI, CKI, IHA, Rmin), as well as the central corneal thickness, on average, significantly decreased. But in 5 patients (all men, mean age 25 years), the Kmax exceeded initial values (from 61.7 to 64.5 diopters), which indicated further progression of keratoconus. The initial values of Kmax in 3 out of 5 of these patients exceeded 57 diopters, which is risk of further progression of keratoconus. Conclusion. With a follow-up period of one year, it was found that CXL in 5 patients (14 %) with keratoconus stages 2-3 turned out to be ineffective. Keywords: keratoconus, photokeratoscopy, corneal collagen crosslinking

Сell model for experimental research in keratoconus pathogenesis

INTRODUCTION: Certain mineral elements dismetabolism is known to play an important part in the pathogenesis of the corneal degenerative and dystrophic diseases, as metalloenzymes participate in connective tissues metabolism affecting their properties. Thus, in keratoconus corneal tissue is depleted in iron, copper and zinc, what could be the underlying cause of cornea biomechanical properties impairment. Keratoconus modeling is complicated and practically not reproducible in animals, therefore cell models elaboration is very much in demand. Definite mineral elements content must be reduced in order to simulate pathological changes specific for keratoconic corneas.&#x0D; PURPOSE: The aim of this study was an elaboration of a cell model suitable for keratoconus pathogenesis research. This goal achieving involved solving the following tasks: 1) to develop a tissue-engineered system that mimic healthy corneal stroma; 2) to develop a technique for selective depletion of the nutrient medium by mineral elements involved in keratoconus pathogenesis; 3) to assess the possibility of the designed tissue-engineered system growth in the depleted nutrient medium.&#x0D; MATERIAL AND METHODS: The study was carried out with the primary culture of human keratocytes, which were used to build tissue-engineered systems of three types: on silicone, on a membrane, without a carrier. Cell cultures morphology was evaluated by light and electron microscopy. The nutrient media were zinc depleted via decationization of fetal bovine serum using two types of ion-exchange resins; mineral elements concentrations were evaluated by means of inductively coupled plasma mass spectrometry.&#x0D; RESULTS: The tissue system engineered without a carrier in form of cell sheet was chosen as the most convenient model. The decationization of the serum by means of Chelex 100 resin was shown to be a successful method for tenfold zinc concentration reduction in the nutrient medium. Keratocytes cultivation in the form of cell sheet on a zinc-depleted medium was successfully approved.&#x0D; CONCLUSION: Elaborated tissue-engineered system could be considered as a model of the corneal stroma under specific for keratoconus conditions of zinc depletion.

Repeatability of Scheimpflug based corneal tomography parameters in advanced keratoconus with thin corneas.

To determine the repeatability limits of corneal tomography parameters in patients with advanced and moderately thin keratoconic corneas to assist in planning thickness-based procedural interventions. Prospective, single-centre, repeatability study. Three tomography scans using the Pentacam AXL were obtained from patients with keratoconus with thinnest corneal thickness (TCT) ≦400 µm (sub-400 group) and compared to those with TCT = 450-500 µm (450-plus group). Eyes with previous crosslinking, intraocular surgery, or acute corneal hydrops were excluded. Eyes were age and gender-matched. The within-subject standard deviations for flat keratometry (K1), steep keratometry (K2), maximal keratometry (Kmax), astigmatism and TCT were used to calculate respective repeatability limits (r). Intra-class correlation coefficients (ICC) were also analysed. The sub-400 group comprised 114 eyes from 114 participants, and the 450-plus group comprised 114 eyes from 114 participants. In the sub-400 group, TCT was amongst the least repeatable parameters (33.92 µm; ICC 0.96), compared with the 450-plus group (14.32 µm; ICC 0.99, p < 0.01). In the sub-400 group, K1 and K2 of the anterior surface were the most repeatable parameters (r 3.79 and 3.22 respectively; ICC 0.97 and 0.98 respectively) compared with the 450-plus group (r 1.17 and 0.92 respectively; and ICC 0.98 and 0.99 respectively, p < 0.01). The repeatability of corneal tomography measurements is significantly reduced in sub-400 keratoconic corneas when compared to 450-plus corneas. Repeatability limits should be carefully considered when surgical interventions are planned for such patients.

Three-years outcomes of simultaneous photorefractive surgery and customized corneal cross-linking for keratoconus.

To report the efficacy of customized cross-linking (CXL) in halting progression of keratoconus when combined with photorefractive procedures. Seven eyes from 7 patients with documented progressive keratoconus were treated with customized CXL (customized ultraviolet-A irradiance pattern centered on the maximum posterior elevation with total energy levels ranging from 5.4 up to 10J/cm2 , and an energy fluence of 9mW/cm2) combined with photorefractive procedures. Four patients underwent simultaneous transepithelial photorefractive keratectomy (T-PRK) plus customized CXL, and three patients underwent simultaneous transepithelial phototherapeutic keratectomy (T-PTK) plus customized CXL. Tomographic parameters (Kmax, pachymetry of the thinnest point and maximal elevation of posterior float and regularization index) and best spectacle-corrected visual acuity (BSCVA) were compared preoperatively and 3years postoperatively. All eyes showed a decrease in the maximal curvature Kmax, and none of eyes showed progression. Six eyes showed a flattening of 3 or more diopters (D). On average, Kmax decreased by - 4.8 ± 2.5 D, and the BSCVA improved by 0.04 ± 0.07 logarithm of the minimal angle of resolution. The mean value of regularization index was 8.7 ± 3.8 D. Mild corneal haze occurred in two eyes, and superficial apical scar occurred in one eye. None of the eyes had a vision-threatening complication. Customized CXL combined with photorefractive procedure (T-PRK/T-PTK) resulted in long lasting flattening effect and strong regularization of keratoconic corneas along with improvement of BSCVA over a 3-year follow-up.

Differences in retinal images quality between normal and subclinical keratoconus and its association to posterior corneal asymmetry.

To compare retinal image quality in subclinical keratoconus and normal eyes using a double-pass aberrometer and to correlate it with posterior surface deformation. Sixty normal corneas were compared to 20 subclinical keratoconus (SKC) corneas. Retinal image quality was assessed using a double-pass system in all the eyes. The objective scatter index (OSI) modulation transfer function (MTF) cutoff, Strehl ratio (SR), and Predicted Visual Acuity (PVA) values at 100%, 20%, and 9% were calculated and compared between the groups. Posterior corneal asymmetry was measured using a combined Placido Dual Scheimpflug Analyzer, and correlations were tested with all optical quality parameters. Significant decrease in optical quality parameters was observed in SKC eyes compared with that in normal eyes. Subclinical KC eyes expressed greater scattering (OSI = 0.66 ± 0.36 vs 0.47 ± 0.26) and reduced contrast images (MTF and SR) than normal eyes, with 38.82 ± 9.4 and 0.22 ± 0.04, and 44.35 ± 7.1 and 0.24 ± 0.04, respectively. The reduction in the image contrast parameters (MTF and SR) was strongly correlated to the level of posterior corneal asymmetry in SKC. The greater the posterior asymmetry, the more affected was the image contrast, with r = -0.63 and -0.59, respectively for MTF and SR. Retinal image quality was significantly more affected in eyes with subclinical keratoconus than in normal eyes. The reduction in optical quality observed in subclinical keratoconus was strongly associated with the increased asymmetry of the posterior cornea.

Motion-Tracking Brillouin Microscopy Evaluation of Normal, Keratoconic, and Post–Laser Vision Correction Corneas

To characterize focal biomechanical differences between normal, keratoconic, and post-laser vision correction (LVC) corneas using motion-tracking Brillouin microscopy. Prospective cross-sectional study. Thirty eyes from 30 patients (10 normal controls [Controls], 10 post-LVC, and 10 stage I or II keratoconus [KC]) had Scheimpflug and motion-tracking Brillouin microscopy imaging using a custom-built device. Mean, maximum (max) and minimum (min) Brillouin shift, spatial standard deviation, and max-min values were compared. Min values were correlated with local Brillouin values at multiple Scheimpflug imaging locations. Mean (P < .0003), min (P < .00001), spatial standard deviation (P < .01), and max-min (P < .001) were significantly different between the groups. In post hoc pairwise comparisons, the best differentiators for group comparisons were mean (P = .0004) and min (P = .000002) for Controls vs KC, min (P = .0022) and max-min (P = .002) for Controls vs LVC, and mean (P = .0037) and min (P = .0043) for LVC vs KC. Min (area under the receiver operating characteristic = 1.0) and mean (area under the receiver operating characteristic = 0.96) performed well in differentiating Control and KC eyes. Min values correlated best with Brillouin shift values at the thinnest corneal point (r2 = 0.871, P = .001) and maximum keratometry value identified in the tangential curvature map (r2 = 0.840, P = .002). Motion-tracking Brillouin microscopy effectively characterized focal corneal biomechanical alterations in LVC and KC and clearly differentiated these groups from Controls. Primary motion-tracking Brillouin metrics performed well in differentiating groups as compared with basic Scheimpflug metrics, in contrast to previous Brillouin studies, and identified focal changes after LVC where prior Brillouin studies did not.

Comparison of corneal biomechanical properties in healthy thin corneas with matched keratoconus eyes.

To compare corneal biomechanical parameters of normal thin corneas with matched keratoconus eyes. Eye Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. Cross-sectional comparative study. Dynamic corneal response parameters of Corvis ST were compared in 61 eyes with keratoconus with 61 matched healthy thin corneas (corneal thinnest point <500 μm), while corneal thickness, biomechanically corrected intraocular pressure, and age were considered covariates. The receiving operator sensitivity curve analysis was used to determine the cutoff point with the highest sensitivity and specificity, and the area under the curve (AUC) for each parameter. All biomechanical parameters were statistically significant between the 2 groups except for the first ( P = .947) and second ( P = .582) applanation length, first ( P = .783) and second ( P = .301) applanation velocity, and deformation amplitude in the highest concavity phase ( P = .106). The highest mean difference between groups (12.89 ± 2.03 mm Hg/mm) was related to the stiffness parameter at the first applanation (SPA1). Although the Corvis biomechanical index and tomographic biomechanical index had the highest detection ability based on their AUC (0.912 and 0.959, respectively), among the standard and combined biomechanical parameters except for keratoconus screening parameters, the highest discriminative ability was related to SPA1 with AUC, sensitivity, and specificity of 0.793, 60.66%, and 90.16%, respectively. Keratoconus corneas were significantly softer compared with healthy thin corneas of matched thickness. Optimal cutoff points close to the maximum value defined for screening parameters limit their clinical use for differentiation purposes in these particular types of cases.