Fitting-Shape-based Strategy for Topography-guided LASIK: A Prospective Study.

PURPOSE: To assess and compare the visual acuity and refractive outcomes of topography-guided laser in situ keratomileusis (LASIK) based on the fitting-shape-based refractive compensated and Phorcides software strategies. METHODS: Consecutive patients who underwent topography-guided LASIK were included in this study. Through double-masked simple randomization, patients were assigned to the Zhang & Zheng Auto-compensate Refraction (ZZ AR) group (the fitting-shape-based refractive compensated strategy using the ZZ AR calculator was used) or the Phorcides group (the topography analysis algorithm in Phorcides software [Phorcides LLC] was used). Only one eye per patient with binocular correction was randomly enrolled. The preoperative and postoperative visual acuities and refraction were analyzed at the 6-month follow-up visit. RESULTS: The ZZ AR and Phorcides groups comprised 156 and 147 eyes, respectively. At the 6-month postoperative follow-up visit, the median (range) absolute residual cylindrical refraction was 0.35 (1.01) and 0.47 (1.63) diopters (D) for the ZZ AR and Phorcides groups, respectively (P < .001). The percentages of patients with residual cylindrical power within 0.25 D were 29.49% and 13.61% for the ZZ AR and Phorcides groups, respectively (P = .001). Based on the percentages of patients with residual cylindrical powers within 0.50 and 1.00 D, the ZZ AR group showed better outcomes (P = .02 and .01). The percentage of patients with visual acuity better than 20/16 was significantly higher for the ZZ AR group than for the Phorcides group (P = .03). CONCLUSIONS: The fitting-shape-based refractive compensated strategy for topography-guided LASIK procedures can better optimize the visual acuity and astigmatic refraction than the Phorcides software strategy. [J Refract Surg. 2024;40(5):e336-e343.].

Comparative Study of Primary SMILE, SMILE Enhancement, and Femtosecond Laser-Assisted LASIK on Higher Order Aberrations and Corneal Densitometry.

PURPOSE: To compare differences in corneal densitometry (CD) and higher order aberrations (HOAs) in eyes that underwent small incision lenticule extraction (SMILE) and femtosecond laser-assisted laser in situ keratomileusis (FS-LASIK) for the treatment of myopia and myopic astigmatism at postoperative months 3, 6, and 12, and to evaluate their changes in a separate cohort of eyes after SMILE enhancement. METHODS: In this prospective, randomized, paired-eye clinical trial, consecutive eligible participants were randomized to undergo SMILE or FS-LASIK in either eye. Main outcome measures were CD and HOAs preoperatively and at 3, 6, and 12 months postoperatively. A separate cohort of consecutive patients who had SMILE and underwent enhancement were also included for comparison. RESULTS: For CD, no significant differences were found between SMILE and FS-LASIK up to month 12. For HOA measured by wavefront aberrometry, both SMILE and FS-LASIK had an increase in total root mean square (RMS) HOAs, spherical aberration (SA), and vertical coma up to month 12. SMILE had an additional increase in vertical quatrefoil, and FS-LASIK had an increase in horizontal coma at month 12. FS-LASIK had higher SA than SMILE, whereas SMILE had higher vertical quatrefoil than FS-LASIK at month 12. Central and posterior zone CD had significantly decreased after SMILE enhancement compared to after primary SMILE up to 2 years after enhancement. RMS HOAs, lower order aberrations, and SA were all increased after SMILE enhancement compared to after primary SMILE. CONCLUSIONS: SMILE induced lower SA but higher vertical quatrefoil than FS-LASIK at 1 year. Both SMILE and FS-LASIK had similar increases in RMS HOAs and vertical coma up to 1 year. There were no differences in CD between both groups. SMILE enhancement additionally had decreased central and posterior CD but greater RMS HOAs and SA compared to primary SMILE. [J Refract Surg. 2024;40(5):e291-e303.].

In Vivo Corneal Biomechanical Response to Three Different Laser Corneal Refractive Surgeries.

PURPOSE: To compare the effects of three common refractive surgeries on corneal biomechanics. METHODS: Two hundred seven patients who had refractive surgery were included in this study, of whom 65 received transepithelial photorefractive keratectomy (tPRK), 73 received femtosecond laser-assisted laser in situ keratomileusis (FSLASIK), and 69 received small incision lenticule extraction (SMILE). Each patient had biomechanical measurements using the Corvis ST (Oculus Optikgeräte GmbH) preoperatively and at 3 and 6 months postoperatively. The measurements included five parameters expected to be associated with corneal biomechanics: deformation amplitude ratio at 2 mm (DAR2), integrated inverse radius (IIR), stiffness parameter at first applanation (SP-A1), highest concavity time (HCT), and the updated stress-strain index (SSIv2). The variations in these parameters postoperatively among the three surgeries, and their relationship with corneal thickness (CCT) and intraocular pressure measured by the Dynamic Contour Tonometer (DCT-IOP) were analyzed. RESULTS: SP-A1 decreased significantly from preoperatively to 3 months postoperatively in all three groups, whereas DAR2 and IIR increased significantly, all indicating stiffness losses. Between 3 and 6 months postoperatively, the results were inconsistent, with DAR2 decreasing (indicating stiffness increases) and IIR increasing (denoting stiffness decreases) in the FS-LASIK and SMILE groups. The decrease in SSIv2 (the only measure of corneal material stiffness) postoperatively was comparatively less pronounced at both 3 and 6 months postoperatively. On the other hand, HCT remained generally stable after all three surgeries. Unlike DAR2, IIR, and SP-A1, the changes postoperatively in stiffness parameters HCT and SSIv2 were independent of the corresponding changes in both DCT-IOP and CCT. CONCLUSIONS: Among the stiffness parameters considered, SSIv2 was not correlated with CCT or DCT-IOP, and holds promise for representing the corneal material stiffness and how it remains largely unaffected by refractive surgeries. Overall, FS-LASIK had the most significant impact on corneal stiffness, followed by SMILE, and finally tPRK. [J Refract Surg. 2024;40(5):e344-e352.].

[Effect of refractive surgery on Maklakov tonometry results]. / Vliyanie keratorefraktsionnoi khirurgii na rezul'taty tonometrii po Maklakovu.

PURPOSE: The study investigates the influence of changes in keratometric parameters after refractive surgery on the results of Maklakov tonometry. MATERIAL AND METHODS: The study examined a total of 61 people (121 eyes). The patients were divided into a control group with no history of surgery (16 people, 31 eyes), a LASIK group (13 people, 26 eyes), a femtosecond-assisted LASIK (FS-LASIK) group (16 people, 32 eyes), and a photorefractive keratectomy (PRK) group (16 people, 32 eyes). The patients underwent standard examination, keratometry (Km), Maklakov tonometry with a 10 g weight, and elastotonometry with 5, 7.5, and 15 g weights. RESULTS: In the LASIK group, the indentation diameter with 5 and 7.5 g weights correlated with Km in the central and near-paracentral zone (r=0.3-0.5). Tonometry with a 10 g weight did not correlate with anything. Tonometry with a 15 g weight inversely correlated with Km in the paracentral points (4 mm) of the strong meridian (r= -0.5 ... -0.7). In the FS-LASIK group, a significant inverse correlation with Km was observed only for the indentation diameter with a 10 g weight in the paracentral (3-4 mm) zone (r= -0.4 ... -0.5). In the PRK group, weak (r<0.4) correlations were found between Km and the indentation diameter of the 7.5 and 10 g weights for the central zone (1-2 mm). No significant correlations were found for 5 and 15 g weights.In the control group, there were practically no correlations for 5 and 7.5 g weights. The indentation diameter of the 10 g weight evenly correlated with Km at all points (r= -0.38 ... -0.60), the indentation of the 15 g weight correlated mainly with the curvature of the horizontal meridian (r= -0.37 ... -0.49). CONCLUSION: Tonometry readings with the 10 g weight are the most dependent on Km in different groups, and the readings with the 5 g weight are the least dependent. LASIK is characterized by the largest scatter of dependencies for weights of different masses, FS-LASIK - by the smallest. Tonometry readings with the 5 g weight correlated with Km only in the LASIK group, and this was the only direct correlation. Considering the inverse nature of most correlations, higher Km may be associated with an overestimation of tonometry results, and lower Km - with its underestimation.

Comparative evaluation of biomechanical changes and aberration profile following accelerated collagen cross-linking using hypo-osmolar and iso-osmolar riboflavin: A prospective study.

PURPOSE: To compare the changes encountered in corneal biomechanics and aberration profile following accelerated corneal collagen cross-linking (CXL) using hypo-osmolar and iso-osmolar riboflavin in corneal thicknesses of <400 and >400 microns, respectively. METHODS: This is a prospective, interventional, comparative study involving 100 eyes of 75 patients with progressive keratoconus. Eyes were divided into two groups based on corneal thickness: group 1 included eyes with a corneal thickness of <400 microns who underwent hypo-osmolar CXL, and group 2 included eyes with a corneal thickness of >400 microns who underwent iso-osmolar CXL. Corneal biomechanical and aberration profiles were evaluated and compared between groups. RESULTS: In group 1, all higher-order aberrations (HOA) except secondary astigmatism significantly decreased from baseline; however, in group 2, only coma and trefoil decreased. The corneal resistance factor and corneal hysteresis significantly improved in both groups, which was significantly greater in group 2 than in group 1. The change in inverse radius, deformation amplitude, and tomographic biomechanical index was significantly improved in group 2 as compared to group 1. CONCLUSION: Improvement in corrected distance visual acuity and decrease in HOA were significantly better in the hypo-osmolar CXL group; however, the improvement in biomechanical strength of the cornea was significantly better in the iso-osmolar group.

Allowable movement of wavefront-guided contact lens corrections in normal and keratoconic eyes.

PURPOSE: The goal was to use SyntEyes modelling to estimate the allowable alignment error of wavefront-guided rigid contact lens corrections for a range of normal and keratoconic eye aberration structures to keep objectively measured visual image quality at or above average levels of well-corrected normal eyes. Secondary purposes included determining the required radial order of correction, whether increased radial order of the corrections further constrained the allowable alignment error and how alignment constraints vary with keratoconus severity. METHODS: Building on previous work, 20 normal SyntEyes and 20 keratoconic SyntEyes were fitted with optimised wavefront-guided rigid contact lens corrections targeting between three and eight radial orders that drove visual image quality, as measured objectively by the visual Strehl ratio, to near 1 (best possible) over a 5-mm pupil for the aligned position. The resulting wavefront-guided contact lens was then allowed to translate up to ±1 mm in the x- and y-directions and rotate up ±15°. RESULTS: Allowable alignment error changed as a function of the magnitude of aberration structure to be corrected, which depends on keratoconus severity. This alignment error varied only slightly with the radial order of correction above the fourth radial order. To return the keratoconic SyntEyes to average levels of visual image quality depended on maximum anterior corneal curvature (Kmax). Acceptable tolerances for misalignment that returned keratoconic visual image quality to average normal levels varied between 0.29 and 0.63 mm for translation and approximately ±6.5° for rotation, depending on the magnitude of the aberration structure being corrected. CONCLUSIONS: Allowable alignment errors vary as a function of the aberration structure being corrected, the desired goal for visual image quality and as a function of keratoconus severity.

The long and short of it: a comprehensive assessment of axial length estimation in myopic eyes from ocular and demographic variables.

BACKGROUND/OBJECTIVES: Axial length, a key measurement in myopia management, is not accessible in many settings. We aimed to develop and assess machine learning models to estimate the axial length of young myopic eyes. SUBJECTS/METHODS: Linear regression, symbolic regression, gradient boosting and multilayer perceptron models were developed using age, sex, cycloplegic spherical equivalent refraction (SER) and corneal curvature. Training data were from 8135 (28% myopic) children and adolescents from Ireland, Northern Ireland and China. Model performance was tested on an additional 300 myopic individuals using traditional metrics alongside the estimated axial length vs age relationship. Linear regression and receiver operator characteristics (ROC) curves were used for statistical analysis. The contribution of the effective crystalline lens power to error in axial length estimation was calculated to define the latter's physiological limits. RESULTS: Axial length estimation models were applicable across all testing regions (p ≥ 0.96 for training by testing region interaction). The linear regression model performed best based on agreement metrics (mean absolute error [MAE] = 0.31 mm, coefficient of repeatability = 0.79 mm) and a smooth, monotonic estimated axial length vs age relationship. This model was better at identifying high-risk eyes (axial length >98th centile) than SER alone (area under the curve 0.89 vs 0.79, respectively). Without knowing lens power, the calculated limits of axial length estimation were 0.30 mm for MAE and 0.75 mm for coefficient of repeatability. CONCLUSIONS: In myopic eyes, we demonstrated superior axial length estimation with a linear regression model utilising age, sex and refractive metrics and showed its clinical utility as a risk stratification tool.

Biomechanical and Vascular Metrics Between Eyes of Patients With Asymmetric Glaucoma and Symmetric Glaucoma.

PRCIS: Corneal hysteresis (CH) and pulsatile ocular blood volume (POBV) were significantly lower in the eye with greater damage in asymmetric glaucoma, without a difference in intraocular pressure (IOP) or central corneal thickness (CCT), and no difference in elastic parameters. OBJECTIVE: To compare biomechanical and vascular metrics between the eyes of patients with asymmetric glaucoma (ASYMM) and those with symmetric glaucoma (SYMM). PATIENTS AND METHODS: Forty-five patients were prospectively recruited and divided into ASYMM, defined as cup-to-disc (C/D) ratio difference >0.1 between eyes and SYMM, with C/D difference ≤0.1. For ASYMM, the smaller C/D was defined as the best eye ("best") and the fellow eye was defined as the worst eye ("worse"). All metrics were subtracted as "worse" minus "best," including the viscoelastic parameter CH, and elastic parameters from the Corvis ST, including stiffness parameter at first applanation, stiffness parameter at highest concavity, integrated inverse radius, deformation amplitude ratio, IOP, CCT, mean deviation (MD), ganglion cell complex (GCC), and POBV were included. Paired t tests were performed between eyes in both groups. Statistical analyses were performed with SAS using a significance threshold of P <0.05. RESULTS: For ASYMM (16 patients), "worse" showed significantly lower CH (-0.76 ± 1.22), POBV (-0.38 ± 0.305), MD (-3.66 ± 6.55), and GCC (-7.9 ± 12.2) compared with "best." No other parameters were significantly different. For SYMM (29 patients), there were no significantly different metrics between eyes. CONCLUSIONS: Lower CH, POBV, GCC, and worse MD were associated with greater glaucomatous damage in asymmetric glaucoma without a difference in IOP or CCT. Lower CH and GCC are consistent with previous studies. POBV, a new clinical parameter that may indicate reduced blood flow, is also associated with greater damage.

Best Indicators for Detecting Keratoconus Progression in Children: A Report From the Shahroud Schoolchildren Eye Cohort Study.

PURPOSE: The purpose of this study was to investigate 3-year changes in keratoconus (KC) indices to determine the indicators of KC progression compared with age-related changes in children aged 6 to 12 years. METHODS: In this report of the Shahroud Schoolchildren Eye Cohort Study, KC was diagnosed based on vision, refraction, tomography, and slitlamp examination findings. KC progression was defined as changes in refractive astigmatism or zonal maximum keratometry (Zonal Kmax-3 mm). Then, 3-year changes (Δ) in vision, refraction, and tomographic indices were compared between progressive KC and normal eyes. The best set of ∆parameters for distinguishing KC progression from age-related changes were determined using the area under curve (AUC). RESULTS: Eighteen KC eyes and 10,422 normal eyes were analyzed. All KC cases showed progression after 3 years. Δindices were statistically different between the 2 groups except corrected distance visual acuity, anterior radius of curvature, irregularity index, and KC percentage index. The best Δindices, in descending order of AUC value, were index of height decentration, Zonal Kmax-3 mm, refractive astigmatism, single point Kmax, and index of vertical asymmetry (all AUC > 0.9), followed by inferior-superior asymmetry, index of surface variance, minimum corneal thickness, index of height asymmetry, KC index, posterior radius of curvature, and Belin/Ambrósio total Deviation (AUC = 0.8-0.9). CONCLUSIONS: According to our findings, changes in index of height decentration, Zonal Kmax-3 mm, refractive astigmatism, single point Kmax, and index of vertical asymmetry are the best indices for detecting KC progression in children younger than 12 years.

Predicting factors for the efficacy of cross-linking for keratoconus.

PURPOSE: To evaluate predictors for success in corneal crosslinking (CXL) for keratoconus in a large cohort and extended follow-up. DESIGN: A retrospective study based on a prospectively built database. METHODS: Participants underwent CXL for keratoconus from 2007 to 2018. Statistical analysis was performed for patients with at least 1-year follow-up. We analyzed effects of CXL type (Epithelium-on or Epithelium-off and Accelerated (9mW/cm2@10min) or Standard (3mW/cm2@30min)) and pre-operative factors including age, gender, baseline LogMAR visual acuity (LogMARpre), maximal corneal power (Kmaxpre), pachymetry, refractive and topographic cylinders, spherical equivalent (SEpre), mean corneal power (MeanK) and follow-up time on outcome measures. The outcome measures were the final change of Kmax (Delta Kmax) and the final change in LogMAR visual acuity (Delta LogMAR). A more negative Delta Kmax or Delta LogMAR represents a favorable effect of crosslinking. RESULTS: 517 eyes had Kmax results, and 385 eyes had LogMAR results with more than one year follow-up. These eyes were included in the study. The mean follow-up time was 2.29 years. Mean Kmax decreased from 54.07±5.99 diopters to 52.84±5.66 diopters (p<0.001), and Mean LogMAR decreased from 0.28±0.20 to 0.25±0.21 (p<0.001). Non-accelerated epithelium-off CXL resulted in greater flattening of Kmax when compared with other protocols. Visual acuity improvement was similar when comparing different CXL protocols. Multivariate analysis showed four factors associated with negative Delta Kmax: high Kmaxpre, high SEpre, high MeanKpre, and non-accelerated procedure. Multivariate analysis showed three factors associated with negative Delta LogMAR: high LogMARpre, high SEpre, and Low MeanKpre. After excluding corneas with Kmaxpre >65 D or Pachymetry<400 microns, multivariate analysis showed that high Kmaxpre, high SEpre, and non-accelerated CXL were associated with negative Delta Kmax while high LogMARpre and high SEpre were associated with negative Delta LogMAR. CONCLUSION: CXL for keratoconus is a highly effective treatment, as evident by its effects on the outcome measures: Delta Kmax and Delta LogMAR. CXL was more successful in eyes with high Kmaxpre, high SEpre, and high LogMARpre, which express disease severity. The non-accelerated epithelium-off protocol was associated with greater flattening of corneal curvature but did not show a better effect on visual acuity as compared to the other CXL protocols.

Changes in corneal densitometry after long-term orthokeratology for myopia and short-term discontinuation.

PURPOSE: To quantify changes in corneal densitometry after long-term orthokeratology treatment in myopic children and to analyze the reversibility one month after discontinuation. METHODS: Seventy-four myopic subjects aged 8-16 years, who wore orthokeratology lenses for two years, were divided into relatively steep- (lens movement within 1.0-1.5 mm, thirty-six participants) and flat-fitting groups (lens movement within 1.5-2.0 mm, thirty-eight participants). Based on refractive errors, they were divided into low and moderate myopia groups (thirty-seven participants in each group). Corneal densitometry was performed using Pentacam (Oculus Optikgeräte GmbH, Wetzlar, Germany) at each follow-up timepoint. Repeated-measures analysis of variance was used to compare the parameters before and after orthokeratology. RESULTS: The corneal densitometry values over the 0-10 mm diameter area increased from 12.84±1.38 grayscale units (GSU) at baseline to 13.59±1.42 GSU after three-month orthokeratology (P = .001) and reached 14.92±1.45 GSU at two years (P < .001). An increase in densitometry began at one month (P = .001) over the 0-2 mm annulus compared with that at three months over the 2-6 mm and 6-10 mm zones (P = .002,.014). The densitometry values significantly increased at three months in the relatively steep-fitting group (P = .003) and at one year in the relatively flat-fitting group (P = .001). After discontinuation of orthokeratology for one month, the values showed no significant decrease. CONCLUSIONS: Long-term orthokeratology treatment causes a small but statistically significant increase in corneal densitometry values. During the first year, the onset of these changes was related to the fitting mode. Corneal densitometry values showed no significant reduction after one-month discontinuation.

Fibrosis Is a Basement Membrane-Related Disease in the Cornea: Injury and Defective Regeneration of Basement Membranes May Underlie Fibrosis in Other Organs.

Every organ develops fibrosis that compromises functions in response to infections, injuries, or diseases. The cornea is a relatively simple, avascular organ that offers an exceptional model to better understand the pathophysiology of the fibrosis response. Injury and defective regeneration of the epithelial basement membrane (EBM) or the endothelial Descemet's basement membrane (DBM) triggers the development of myofibroblasts from resident corneal fibroblasts and bone marrow-derived blood borne fibrocytes due to the increased entry of TGF beta-1/-2 into the stroma from the epithelium and tears or residual corneal endothelium and aqueous humor. The myofibroblasts, and disordered extracellular matrix these cells produce, persist until the source of injury is removed, the EBM and/or DBM are regenerated, or replaced surgically, resulting in decreased stromal TGF beta requisite for myofibroblast survival. A similar BM injury-related pathophysiology can underly the development of fibrosis in other organs such as skin and lung. The normal liver does not contain traditional BMs but develops sinusoidal endothelial BMs in many fibrotic diseases and models. However, normal hepatic stellate cells produce collagen type IV and perlecan that can modulate TGF beta localization and cognate receptor binding in the space of Dissé. BM-related fibrosis is deserving of more investigation in all organs.

Ten-year longitudinal investigation of astigmatism: The Yamagata Study (Funagata).

Despite numerous investigations into ocular or corneal astigmatism, the dynamic nature of astigmatism remains poorly understood. To reveal potential associations between age and astigmatism, 264 Japanese participants who underwent systemic and ophthalmological examinations in Funagata Town (Yamagata Prefecture, Japan) were evaluated over a 10-year period. Astigmatism was evaluated with regard to the cylinder power, cylinder axis, and vector analyses. Whereas the refractive cylinders showed age-related increases in patients in their 40s to 60s, the corneal cylinders did not change over 10 years. Nevertheless, cylindrical axis of the cornea demonstrated a continuous shift toward against-the-rule (ATR) astigmatism. Vector analyses revealed that the astigmatic shift toward ATR progressed continually after patients reached their 40s, although the shift did not accelerate with age. These novel insights may pave the way for the development of potential strategies for vision correction, including refractive surgeries, and vision-quality maintenance in the elderly.

Toric Intraocular Lens Calculation Considering Anterior Surgically Induced Astigmatism and Posterior Corneal Astigmatism.

PURPOSE: To evaluate the prediction error (PE) after applying the Abulafia-Koch formula in an online calculator with and without consideration of anterior corneal surgically induced astigmatism (SIACornea). METHODS: SIACornea models were calculated with a historical database of 204 right eyes (REs) from a single surgeon, either for manual (2.2 mm) or femtosecond (2.5 mm) temporal clear corneal incisions. PE was assessed in 58 REs operated by the same surgeon with a monofocal toric IOL and calculated, considering the PCA estimation in an online calculator with the combination of each one of the following SIACornea calculation approaches: (A) considering only significant centroids after stratification, (B) all centroids after stratification and (C) a single centroid without stratification. RESULTS: The consideration of all centroids resulted in an underestimation of SIACornea in cases of preoperative against-the-rule astigmatism (ATR-A) and an overestimation in with-the-rule astigmatism (WTR-A). After stratification, SIACornea was only significant in preoperative ATR and oblique astigmatism cases for femtosecond incisions. PE considering PCA only was 0.03@160º. The combination with SIACornea resulted in a WTR-A surprise in preoperative ATR-A and WTR-A, however only being significant for preoperative ATR-A in calculation approaches B (0.29@84º) and C (0.21@80º). SIACornea addition to PCA estimation only reduced the centroid for oblique preoperative astigmatism. CONCLUSIONS: Surgeons should consider the calculation of the SIACornea after stratification by astigmatism type when using the same incision location (i.e. temporal). However, SIACornea derived from the anterior corneal surface should not be combined with PCA estimation for IOL power calculations.

Reliability analysis of successive Corneal Visualization Scheimpflug Technology measurements in different keratoconus stages.

BACKGROUND: This study assesses the reliability of successive corneal biomechanical response measurements by the Corneal Visualization Scheimpflug Technology (CST, Corvis ST® , Oculus Optikgeräte, Wetzlar, Germany) in different keratoconus (KC) stages. METHODS: A total of 173 eyes (15 controls: 15 eyes, and 112 KC patients: stages 1|1-2|2|2-3|3|3-4|4, n = 26|16|36|18|31|26|5 according to Topographical KC Classification, TKC) were repeatedly examined five times with the CST, each after repositioning the patient's head and re-adjusting the device. Tomographical analysis (Pentacam HR® ; Oculus, Wetzlar, Germany) was performed once before and once after CST measurements. Outcome measures included (1) A1 velocity, (2) deformation amplitude (DA) ratio 2 mm, (3) integrated radius, (4) stiffness parameter A1 and (5) Ambrósio relational thickness to the horizontal profile (ARTh). The Corvis Biomechanical Index (CBI) is reported to be extracted out of these parameters. Mean values of the five measurements and Cronbach's α were calculated as a measure for reliability. RESULTS: Ambrósio relational thickness to the horizontal profile and SPA1 were significantly higher in controls (534|123) compared to TKC1 (384|88), TKC2 (232|66), TKC3 (152|55) and TKC4 (71|27; p < 0.0001). The other parameters were similar in controls and TKC1 (A1 velocity: 0.148|0.151 m/s; integrated radius: 8.2|8.6 mm-1 ), but significantly higher in TKC stages 2 to 4 (DA ratio 2 mm: 5.5|6.3|8.0; A1 velocity: 0.173|0.174|0.186 m/second; integrated radius: 10.9|12.8|19.0 mm-1 ; p < 0.0001). All parameters proved to be highly reliable (Cronbach's α ≥ 0.834) and the corneal tomography remained unaffected. CONCLUSIONS: The individual parameters included in the CBI (consisting of ARTh, SPA1, DA ratio 2 mm, A1 velocity and integrated radius) are highly reliable but differ KC stage-dependently.

Topical retinoic acid induces corneal strengthening by upregulating transglutaminase 2 in murine cornea.

Transglutaminase 2 (TG2) is the most abundant crosslinking enzyme in murine and human cornea, while retinoids are well-known inducers of TG2 expression. This study aims to determine if the retinoic acid supplementation can increase corneal stiffness by crosslinking through upregulating the corneal TG2 expression. The right eyes of C57BL/6 mice were treated with 2 × 10-2M retinol palmitate (VApal) eyedrops or control eyedrops and hold for 30 min, once a day for 28 consecutive days. The WB and qPCR results showed increased expression of TG2 in murine cornea with the prolongation of VApal eyedrop application. After 28 days of VApal eyedrop treatment, the increased TG2 were found catalytically active and distributed in corneal epithelium and stroma as detected by 5-(biotinamido) pentylamine (5-BP) incorporation method and immunofluorescence staining. The transmission electron microscope image revealed that VApal treated cornea manifested with increased collagen density in anterior and middle layer of stroma. The higher elastic module was found among VApal treated cornea by nano-indentation test. In cultured corneal epithelial cells and keratocytes, all-trans retinoid acid (ATRA) treatment increased the content of TG2 in cell lysis and in culture medium. These results indicate that retinoic acid induce the reinforcement of the cornea by TG2 mediated crosslinking via increasing the TG2 expression in corneal epithelium and keratocyte. As TG2 was found to be less in the cornea of keratoconus patients in several RNA-sequencing studies, retinoic acid could serve as a non-invasive prevention method for keratoconus progression.

Corneal Nerve Fiber and Sensitivity Loss After Repeated Intravitreal Anti-VEGF Injections: An In Vivo Confocal Microscopy Study.

PURPOSE: The purpose of this study was to investigate corneal sensation, subbasal nerve plexus (SBNP), and ocular surface symptoms in patients who underwent multiple intravitreal antivascular endothelial growth factor (anti-VEGF) injections for age-related macular degeneration (AMD) and diabetic macular edema (DME). METHODS: Forty patients with previous anti-VEGF intravitreal injections (20 AMD and 20 DME) and 30 healthy controls were included in this study. In vivo corneal confocal microscopy (IVCM) of the SBNP, corneal sensitivity measurement with a Cochet-Bonnet esthesiometer, noninvasive tear break-up times, and ocular surface disease score index (OSDI) calculation were performed for each participant. Corneal nerve fiber density, corneal nerve branch density, total length of all nerve fibers, corneal total branch density, corneal nerve fiber area, corneal nerve fiber width, and corneal nerve fiber fractal dimension parameters were obtained by automatic digital analysis. RESULTS: Corneal nerve fiber density, corneal nerve branch density, total length of all nerve fibers, and corneal nerve fiber fractal dimension in IVCM imaging and corneal sensitivity were significantly decreased in both AMD and DME groups compared with the control group. Corneal nerve fiber width and OSDI scores were significantly increased in AMD and DME groups compared with the control group. None of the IVCM parameters were significantly different between AMD and DME groups. Corneal sensitivity was decreased in patients with DME compared with patients with AMD. Tear break-up time was not different among the groups. CONCLUSIONS: Corneal SBNP parameters were affected, corneal sensitivity was decreased, and OSDI scores were increased in patients with multiple intravitreal anti-VEGF injections. IVCM parameters were not significantly different between AMD and DME groups.

Bilateral Increase of Matrix Metalloproteinase-9 Expression in Tears After the Unilateral Decrease of Corneal Sensitivity.

PURPOSE: The purpose of this study is to analyze bilateral changes of matrix metalloproteinase-9 (MMP-9) expression in the tear film in patients with unilateral neurotrophic keratitis. METHODS: We included 24 eyes from 24 subjects with normal corneal sensitivity according to Cochet-Bonnet corneal esthesiometry in the control group and 25 subjects with the unilateral neurotrophic keratitis in the unilateral decrease of corneal sensitivity (UDCS) group. The expression of MMP-9 in tears was assessed using point-of-care immunoassay. The clinical parameters including meibomian gland plugging, quality of the secreted meibum, tear secretion using Schirmer I without anesthesia, and corneal erosions were evaluated among the control, affected, and contralateral unaffected eyes in the UDCS group. RESULTS: Tear MMP-9 grades in affected (2.5 ± 1.0) and contralateral eyes (2.6 ± 0.9) in the UDCS group were higher than those in control eyes (1.5 ± 0.7, P = 0.0003 and P = 0.0006, respectively). The lacrimal secretion decreased in the affected eyes but preserved in the contralateral eyes. There was no difference in corneal erosion scores between control eyes and contralateral eyes in the UDCS group. Tear MMP-9 grades in the contralateral eyes were significantly correlated with the meibum quality grades in the contralateral eyes (r = 0.525 and P = 0.025). CONCLUSIONS: Patients with the unilateral neurotrophic keratitis demonstrated a significant bilateral increase of the MMP-9 expression in the tear film as compared with controls. Despite the tearing reflex and corneal surface barrier being preserved in the unaffected contralateral eyes, it is necessary to pay attention to the possible attenuation of meibomian gland function in the opposite eyes as well.

Association between Iris Biological Features and Corneal Biomechanics in Myopic Eyes.

PURPOSE: Iris biological features such as surface features and profile characteristics reflected the development of iris stroma and microvessels. Iris vessels and microcirculation are still lack of effective detection methods, and we can directly observe only the iris surface biological characteristics. This cross-sectional study evaluated the association between iris surface biological features and corneal biomechanics in young adults with myopia. METHODS: We recruited 152 patients with myopia aged ≥18 years, from the Eye Hospital of Wenzhou Medical University, who had complete Corneal Visualization Scheimpflug Technology (Corvis ST) data and graded iris surface features. Iris surface features included crypts, furrows, and color measured from digital slit lamp images. The biomechanical properties of the cornea were assessed using Corvis ST. Only 1 eye of each participant was randomly selected for analysis. Associations between the iris surface features and corneal biomechanics were analyzed using linear regression models. The grade of iris crypts, furrows, and color and corneal biomechanical parameters measured with Corvis ST was the main outcome measures. RESULTS: The iris crypts were significantly associated with deflection amplitude at the first applanation (A1 DLA, ß = 0.001, P = 0.013), A1 delta arc length (A1 dArcL) (ß = -0.001, P = 0.01), maximum delta arc length (dArcLM) (ß = -0.004, P = 0.03), and stiffness at the first applanation (SP-A1) (ß = -2.092, P = 0.016). The iris furrows were only associated with integrated radius (ß = -0.212, P = 0.025). Iris color was found not related with corneal biomechanical parameters measured via Corvis ST. CONCLUSIONS: Iris surface features were associated with corneal biomechanical properties in myopic eyes; more iris crypts were associated with lower corneal stiffness while more extensive furrows were related with higher corneal stiffness. Iris crypts and furrows may provide useful information on corneal biomechanical properties in myopic eyes.

Keratoconus enlargement as a predictor of keratoconus progression.

Numerous approaches have been designated to document progression in keratoconus, nevertheless there is no consistent or clear definition of ectasia progression. In this present study, we aim to evaluate Keratoconus Enlargement (KCE) as a parameter to document ectasia progression. We define KCE as an increase of more than 1D in the anterior curvature of non-apical corneal areas. We have designed a longitudinal study in 113 keratoconic eyes to assess keratoconus progression. KCE was compared with variables commonly used for detection of keratoconus progression like Kmax, Km, K2, PachyMin, D-Index, Corneal Astigmatism and PRC of 3.0 mm centered on the thinnest point. The variations of keratometric readings, D-index and ELEBmax showed positive associations with KCE. Evaluating the performance of Kmax, D-index and KCE as isolated parameters to document keratoconus progression we found a sensitivity of 49%, 82% and 77% and a specificity of 100%, 95% and 66% to detect keratoconus progression (p < 0.001 for all). This difference in sensitivity can be explained by the changes in keratoconus outside the small area represented by Kmax. The inclusion of KCE should be considered in the evaluation of keratoconus progression in conjunction with other variables to increase the reliability of our clinical evaluation.