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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

A Hypothalamic-Controlled Neural Reflex Promotes Corneal Inflammation.

Purpose: To test whether an acute corneal injury activates a proinflammatory reflex, involving corneal sensory nerves expressing substance P (SP), the hypothalamus, and the sympathetic nervous system. Methods: C57BL6/N (wild-type [WT]) and SP-depleted B6.Cg-Tac1tm1Bbm/J (TAC1-KO) mice underwent bilateral corneal alkali burn. One group of WT mice received oxybuprocaine before alkali burn. One hour later, hypothalamic neuronal activity was assessed in vivo by magnetic resonance imaging and ex vivo by cFOS staining. Some animals were followed up for 14 days to evaluate corneal transparency and inflammation. Tyrosine hydroxylase (TH), neurokinin 1 receptor (NK1R), and neuronal nitric oxide synthase (nNOS) expression was assessed in brain sections. Sympathetic neuron activation was evaluated in the superior cervical ganglion (SCG). CD45+ leukocytes were quantified in whole-mounted corneas. Noradrenaline (NA) was evaluated in the cornea and bone marrow. Results: Alkali burn acutely induced neuronal activation in the trigeminal ganglion, paraventricular hypothalamus, and lateral hypothalamic area (PVH and LHA), which was significantly lower in TAC1-KO mice (P < 0.05). Oxybuprocaine application similarly reduced neuronal activation (P < 0.05). TAC1-KO mice showed a reduced number of cFOS+/NK1R+/TH+ presympathetic neurons (P < 0.05) paralleled by higher nNOS expression (P < 0.05) in both PVH and LHA. A decrease in activated sympathetic neurons in the SCG and NA levels in both cornea/bone marrow and reduced corneal leukocyte infiltration (P < 0.05) in TAC1-KO mice were found. Finally, 14 days after injury, TAC1-KO mice showed reduced corneal opacity and inflammation (P < 0.05). Conclusions: Our findings suggest that stimulation of corneal sensory nerves containing SP activates presympathetic neurons located in the PVH and LHA, leading to sympathetic activation, peripheral release of NA, and corneal inflammation.

Prevalence of corneal arcus and associated factors in a German population-Results from the Gutenberg Health Study.

PURPOSE: We aimed to determine the prevalence of corneal arcus and to identify associated factors in the general population of Germany. METHODS: The Gutenberg Health Study (GHS) is a population-based cohort study in Germany, which includes an ophthalmological assessment. Refraction, distance-corrected visual acuity, non-contact tonometry and anterior segment imaging were performed for the five-year follow-up examination. Anterior segment photographs were graded for the presence of corneal arcus. Prevalence estimates were computed, and multivariable logistic regression analysis was applied to determine associated factors for corneal arcus including sex, age, spherical equivalent, central corneal thickness, intraocular pressure (IOP), socio-economic status, smoking, BMI, systolic and diastolic arterial blood pressure, HbA1c, HDL-C, LDL-C, triglyceride, and lipid modifying agents. RESULTS: A total of 9,850 right and 9,745 left eyes of 9,858 subjects (59.2±10.8 years), 49.0% females were included in this cross-sectional analysis. 21.1% of men (95%-CI: 20.0%- 22.3%) had a corneal arcus in at least one eye, and 16.9% (95%-CI: 15.9%- 18.0%) of women. In multivariable analyses, the presence of corneal arcus was associated with male gender (OR = 0.54 for female, p<0.0001), higher age (OR = 2.54 per decade, p<0.0001), smoking (OR = 1.59, p<0.0001), hyperopia (OR = 1.05 per diopter, p<0.0001), thinner cornea (OR = 0.994 per µm, p<0.0001), higher IOP (OR = 1.02, p = 0.039), higher HDL-C-level (OR = 2.13, p<0.0001), higher LDL-C-level (OR = 1.21, p<0.0001), and intake of lipid modifying agents (OR = 1.26, p = 0.0001). Arcus was not associated with socio-economic status, BMI, arterial blood pressure, and HbA1c. CONCLUSIONS: Corneal arcus is a frequent alteration of the cornea in Germany and is associated with ocular parameters and systemic parameters of dyslipidemia.

Collagen V insufficiency in a mouse model for Ehlers Danlos-syndrome affects viscoelastic biomechanical properties explaining thin and brittle corneas.

Ehlers-Danlos syndrome (EDS) is a genetic disease leading to abnormalities in mechanical properties of different tissues. Here we quantify corneal biomechanical properties in an adult classic EDS mouse model using two different measurement approaches suited for murine corneal mechanical characterization and relate differences to stromal structure using Second Harmonic Generation (SHG) microscopy. Quasi-static Optical Coherence Elastography (OCE) was conducted non-invasively during ambient pressure modulation by - 3 mmHg. 2D-extensometry measurements was conducted invasively consisting of a pre-conditioning cycle, a stress-relaxation test and a rupture test. In a total of 28 eyes from a Col5a1+/- mouse model and wild-type C57BL/6 littermates (wt), Col5a1+/- corneas were thinner when compared to wt, (125 ± 11 vs 148 ± 10 µm, respectively, p < 0.001). Short-term elastic modulus was significantly increased in OCE (506 ± 88 vs 430 ± 103 kPa, p = 0.023), and the same trend was observed in 2D-extensometry (30.7 ± 12.1 kPa vs 21.5 ± 5.7, p = 0.057). In contrast, in stress relaxation tests, Col5a1+/- corneas experienced a stronger relaxation (55% vs 50%, p = 0.01). SHG microscopy showed differences in forward and backward scattered signal indicating abnormal collagen fibrils in Col5a1+/- corneas. We propose that disturbed collagen fibril structure in Col5a1+/- corneas affects the viscoelastic properties. Results presented here support clinical findings, in which thin corneas with global ultrastructural alterations maintain a normal corneal shape.

Repeatability and comparability of the Galilei-G4 and Cassini in measuring corneal power and astigmatism in normal and post-refractive surgery eyes.

To assess the repeatability and comparability of the Galilei G4 versus the Cassini topographer in post-refractive eyes and in normal eyes, including older patients representative of an initial cataract evaluation. Simulated keratometric (simK), total corneal and posterior corneal power and astigmatism were evaluated in both post-refractive and normal eyes. Repeatability was measured by calculating within-subject standard deviation (Sw), coefficient of variation (CoV), and intraclass correlation coefficient (ICC). Vector analyses and Bland-Altman plots were employed to assess agreement between devices. We studied 32 subjects with a history of refractive surgery and 32 subjects without a history of refractive surgery undergoing cataract surgery. The mean age was 55 ± 18.5 years and the age range was 21.5-91.5 years. In non-refractive and post-refractive eyes, the ICC was > 0.9 (P < 0.001) for all corneal powers and for simK and total corneal astigmatism for both analyzers. The ICC for posterior corneal astigmatism magnitude using the Galilei was 0.62 and 0.67 and for the Cassini 0.55 and 0.38 in normal and post-refractive eyes, respectively. In both post-refractive and normal eyes, the Galilei G4 and Cassini analyzers have high repeatability in simK, total, and posterior corneal power and low repeatability for posterior corneal astigmatism.

Biomechanical Glaucoma Factor and Corneal Hysteresis in Treated Primary Open-Angle Glaucoma and Their Associations With Visual Field Progression.

Purpose: To investigate the relationship between biomechanical glaucoma factor (BGF) measured with Corvis ST and glaucomatous visual field (VF) progression, compared to corneal hysteresis (CH) measured with ocular response analyzer using a longitudinal dataset of primary open-angle glaucoma (POAG). The discriminative powers of BGF and CH were also compared using a cross-sectional dataset. Methods: The longitudinal dataset included 166 POAG eyes. The rate of VF change during the follow-up period was evaluated using the mean of 52 pointwise total deviations in the Humphrey 24-2 field test. Variables associated with the VF progression rate were identified from BGF, CH, age, baseline VF severity, and intraocular pressure during the VF follow-up period by identifying the optimal model. The cross-sectional dataset included 68 POAG eyes and 68 healthy eyes. Using this dataset, the area under the curve (AUC) values of the receiver-operating curve were compared between CH and BGF. Results: The optimal multivariate linear mixed model to describe the VF rate included age and CH, but not BGF. Between POAG and healthy eyes, CH was statistically different (P < 0.001), although this was not the case with BGF. The AUC values were 0.61 and 0.71 for BGF and CH, respectively (P = 0.027). Conclusions: CH, but not BGF, was associated with VF progression in POAG patients under treatment. BGF was not useful to discriminate POAG between treated and normal eyes.

PEDF Gene Deletion Disrupts Corneal Innervation and Ocular Surface Function.

Purpose: The cornea is richly innervated by the trigeminal ganglion (TG) and its function supported by secretions from the adjacent lacrimal (LG) and meibomian glands (MG). In this study we examined how pigment epithelium-derived factor (PEDF) gene deletion affects the cornea structure and function. Methods: We used PEDF hemizygous and homozygous knockout mice to study effects of PEDF deficiency on corneal innervation assessed by beta tubulin staining, mRNA expression of trophic factors, and PEDF receptors by adjacent supporting glands, corneal sensitivity measured using a Cochet-Bonnet esthesiometer, and tear production using phenol red cotton thread wetting. Results: Loss of PEDF was accompanied by reduced corneal innervation and sensitivity, increased corneal surface injury and tear production, thinning of the corneal stroma and loss of stromal cells. PEDF mRNA was expressed in the cornea and its supporting tissues, the TG, LG, and MG. Deletion of one or both PEDF alleles resulted in decreased expression of essential trophic support in the TG, LG, and MG including nerve growth factor, brain-derived neurotrophic growth factor, and GDNF with significantly increased levels of NT-3 in the LG and decreased EGF expression in the cornea. Decreased transcription of the putative PEDF receptors, adipose triglyceride lipase, lipoprotein receptor-related protein 6, laminin receptor, PLXDC1, and PLXDC2 was also evident in the TG, LG and MG with the first three showing increased levels in corneas of the Pedf+/- and Pedf-/- mice compared to wildtype controls. Constitutive inactivation of ERK1/2 and Akt was pronounced in the TG and cornea, although their protein levels were dramatically increased in Pedf-/- mice. Conclusions: This study highlights an essential role for PEDF in corneal structure and function and confirms the reported rescue of exogenous PEDF treatment in corneal pathologies. The pleiotropic effects of PEDF deletion on multiple trophic factors, receptors and signaling molecules are strong indications that PEDF is a key coordinator of molecular mechanisms that maintain corneal function and could be exploited in therapeutic options for several ocular surface diseases.

The Association between Fourier Parameters and Clinical Parameters in Myopic Children Undergoing Orthokeratology.

Purpose: To explore how Fourier parameters are associated with axial length growth (ALG) and clinical parameters in children who underwent orthokeratology.Materials and Methods: A total of 267 children received orthokeratology. Baseline cycloplegic autorefraction was performed. Axial length was measured at baseline and one year after the lens dispatch, and the difference was defined as ALG. Corneal topography was performed at the same two visits. Central treatment zone (CTZ) was identified from the difference between the two tangential maps, and its center distance to corneal center was defined as decentration. A relative refractive corneal power (RCRP) map was derived by subtracting the center value from every point on the one-year axial map. It was decomposed into 3 Fourier components: a mean (F0), a single-cycle sinewave (F1), and a double-cycle sinewave (F2). Linear regressions were used to reveal the association between ALG and these parameters.Results: At baseline, the age was 10.18 ± 1.48 year, spherical equivalent (SE) was - 3.10 ± 1.15D, astigmatism was 1.17 ± 0.58D, and axial length was 24.69 ± 0.81 mm. The mean ALG was 0.181 ± 0.22 mm. In multiple regression, ALG was negatively associated with F1 (p < .001), not F0 and F2. Amplitude-wise, F0 and F1 were correlated with decentration (p < .01) and SE (p < .01), and F2 was associated with astigmatism (p < .001). Direction-wise, F1 was correlated with decentration (p < .001) and F2 was associated with astigmatism (p < .001).Conclusions: Among Fourier parameters, F0 and F1 were negatively associated with ALG in myopic children undergoing orthokeratology. Their associations to SE and CTZ decentration may partially explain the effect on ALG retardation.