Biomechanical properties measured with dynamic Scheimpflug analyzer in central serous chorioretinopathy.

PURPOSE: Recent evidence suggests that venous congestion at the vortex vein significantly contributes to the development of central serous chorioretinopathy (CSCR), and sclera is observed to be thicker in affected eyes. This study aims to investigate whether eyes with CSCR exhibit stiff corneas, measured using Corneal Visualization Scheimflug Technology (Corvis ST), which may serve as an indicator of scleral stiffness. METHODS: This retrospective case-control study comprises 52 eyes from 33 patients diagnosed with CSCR and 52 eyes from 32 normal controls without CSCR. We compared biomechanical parameters measured with Corvis ST and anterior scleral thickness measured using anterior segment swept-source optical coherence tomography between the two groups. RESULTS: Age, sex, axial length, intraocular pressure, and central corneal thickness showed no significant differences between the two groups (p > 0.05, linear mixed model). Three biomechanical parameters-peak distance, maximum deflection amplitude, and integrated inverse radius-indicated less deformability in CSCR eyes compared to control eyes. The stress-strain index (SSI), a measure of stiffness, and anterior scleral thickness (AST) at temporal and nasal points were significantly higher in the CSCR eyes. SSI and AST were not correlated, yet both were significantly and independently associated with CSCR in a multivariate logistic regression model. CONCLUSIONS: Eyes affected by CSCR have stiffer corneas, irrespective of thicker scleral thickness. This suggests that stiffer sclera may play a role in the pathogenesis of CSCR.

Corneal biomechanics are not exclusively compromised in high myopia.

INTRODUCTION: Research assuming linearity has concluded that corneal biomechanics are compromised in high myopia. We investigated whether this assumption was appropriate and re-examined these associations across different levels of myopia. METHODS: Myopic (spherical equivalent refraction, SER ≤ -0.50 D) eyes of 10,488 adults aged 40-69 years without any history of systemic and ocular conditions were identified in the UK Biobank. Ordinary least squares (OLS) regression was employed to test the linear association between corneal hysteresis (CH) or corneal resistance factor (CRF), separately, and SER while controlling for age, sex, corneal radius and intraocular pressure. Quantile regression (QR) was used to test the same set of associations across 49 equally spaced conditional quantiles of SER. RESULTS: In OLS regression, each standard deviation (SD) decrease in CH and CRF was associated with 0.08 D (95% CI: 0.04-0.12; p < 0.001) and 0.10 D (95% CI: 0.04-0.15; p < 0.001) higher myopia, respectively. However, residual analysis indicated that the linearity assumption was violated. QR revealed no evidence of a significant association between CH/CRF and SER in low myopia, but a significant (p < 0.05) positive association became evident from -2.78 D (0.06 and 0.08 D higher myopia per SD decrease in CH and CRF). The magnitude of association increased exponentially with increasing myopia: in the -5.03 D quantile, every SD decrease in CH and CRF was associated with 0.17 D (95% CI: 0.08-0.25; p < 0.001) and 0.21 D (95% CI: 0.10-0.31; p < 0.001) higher myopia. In the -8.63 D quantile, this further increased to 0.54 D (95% CI: 0.33-0.76; p < 0.001) and 0.67 D (95% CI: 0.41-0.93; p < 0.001) higher myopia per SD decrease in CH and CRF. CONCLUSIONS: Corneal biomechanics appeared compromised from around -3.00 D. These changes were observed to be exponential with increasing myopia.

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.

Effect of Corneal and Lens Eccentricity Difference on Rigid Corneal Lens Treatment in Patients With Keratoconus.

OBJECTIVE: To evaluate the effects of rigid corneal lenses (RCL) in patients with keratoconus, based on eccentricity. METHODS: Eighty-four eyes from 84 patients were included in this retrospective comparative study. Based on the median value of eccentricity difference between the cornea and back surface of the RCL, the patients were divided into groups 1 (<0.08) and 2 (≥0.08). Visual acuity, refractive index, and corneal topography indices were compared before and three months after lens use. RESULTS: Visual acuity, astigmatism, refractive error, corneal curvature, and corneal thickness improved significantly in both groups. Apical power and anterior elevation improved significantly in group 1, with small differences in eccentricity, but not in group 2. Changes in apical power before and after lens use were significantly different between the two groups. CONCLUSION: The RCL was effective for the cornea of keratoconus, especially when the prescription was made with a small difference in eccentricity.

[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.

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.

Signaling Lymphocytic Activation Molecule Family-7 Alleviates Corneal Inflammation by Promoting M2 Polarization.

BACKGROUND: Signaling lymphocytic activation molecule family-7 (SLAMF7) functions as an immune checkpoint molecule on macrophages in antitumor immunity. However, its role in bacterial infection remains largely unknown. METHODS: Bone marrow-derived macrophages (BMDMs) isolated from wild-type (WT) or SLAMF7 knockout (KO) mice were infected with bacteria or treated with lipopolysaccharide/interferon-γ to investigate the expression and function of SLAMF7 in macrophage polarization. A Pseudomonas aeruginosa keratitis murine model was established to explore the effect of SLAMF7 on P. aeruginosa keratitis using WT vs SLAMF7 KO mice, or recombinant SLAMF7 vs phosphate-buffered saline-treated mice, respectively. RESULTS: SLAMF7 expression was enhanced on M1-polarized or bacterial-infected macrophages, and infiltrating macrophages in P. aeruginosa-infected mouse corneas. SLAMF7 promoted M2 polarization by inducing STAT6 activation. In vivo data showed that SLAMF7 KO aggravated, while treatment with recombinant SLAMF7 alleviated, corneal inflammation and disease severity. In addition, blockage of M2 polarization by Arg-1 inhibitor abrogated the effect of recombinant SLAMF7 in disease progression. CONCLUSIONS: SLAMF7 expression in macrophages was induced upon M1 polarization or bacterial infection and alleviated corneal inflammation and disease progression of P. aeruginosa keratitis by promoting M2 polarization. These findings may provide a potential strategy for the treatment of P. aeruginosa keratitis.

Corneal Stiffness Parameters Are Predictive of Structural and Functional Progression in Glaucoma Suspect Eyes.

PURPOSE: To investigate corneal stiffness parameters (SPs) as predictors of future progression risk in glaucoma suspect eyes. DESIGN: Prospective, longitudinal study. PARTICIPANTS: Three hundred seventy-one eyes from 228 primary open-angle glaucoma suspects, based on optic disc appearance, with normal baseline Humphrey Visual Field (HVF; Carl Zeiss Meditec) results. METHODS: Baseline corneal SPs were measured using Corvis ST (Oculus Optikgeräte GmbH). Participants were followed up every 6 months with clinical examination, HVF testing, and OCT. The baseline SP at first applanation (SP-A1) and highest concavity predicted the prospective outcome measures. MAIN OUTCOME MEASURES: Structural progression was measured by the OCT rate of thinning of the retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GCIPL). Functional progression was assessed by permutation analysis of pointwise linear regression criteria on HVF testing. RESULTS: Stiffness parameters correlated positively with central corneal thickness (CCT), which was adjusted for in all analyses. A higher SP-A1, suggestive of a stiffer cornea, was associated with a faster rate of RNFL thinning (P < 0.001), synergistic with thinner CCT (P = 0.004) over a mean follow-up of 4.2 years. Eyes with higher SP-A1 and thinner CCT (thin and stiff corneas) showed accelerated RNFL thinning by 0.72 µm/year relative to eyes with lower SP-A1 and thicker CCT (95% confidence interval [CI], 0.17-1.28; P = 0.011) and were at 2.9-fold higher likelihood of fast RNFL progression of more than 1 µm/year (95% CI, 1.4-6.1; P = 0.006). Consistent results also were observed with GCIPL thinning. Furthermore, a higher SP-A1 was associated with a greater risk of visual field progression (P = 0.002), synergistic with thinner CCT (P = 0.010). Eyes with higher SP-A1 and thinner CCT were at 3.7-fold greater risk of visual field progression relative to eyes with thicker CCT and lower SP-A1 (95% CI, 1.3-10.5; P = 0.014). CONCLUSIONS: Glaucoma suspect eyes with higher corneal SPs and lower CCT, suggestive of thin and stiff corneas, are at greater risk of progression. Corneal SPs seem to act synergistically with CCT as risk factors for glaucoma progression.

Ectatic diseases.

Ectatic corneal disease (ECD) comprises a group of disorders characterized by progressive thinning and subsequent bulging of the corneal structure. Different phenotypes have been recognized, including keratoglobus, pellucid marginal degeneration (PMD), and keratoconus (KC). Keratoconus has been widely investigated throughout the years, but the advent of laser refractive surgery boosted an immediate need for more knowledge and research about ectatic diseases. This article discusses nomenclature of ectatic disease, etiology and pathogenesis, along with treatment options, with special focus ok KC and forme fruste keratoconus.

Corneal angiogenic privilege and its failure.

The cornea actively maintains its own avascular status to preserve its ultimate optical function. This corneal avascular state is also defined as "corneal angiogenic privilege", which results from a critical and sensitive balance between anti-angiogenic and pro-angiogenic mechanisms. In our review, we aim to explore the complex equilibrium among multiple mediators which prevents neovascularization in the resting cornea, as well as to unveil the evolutive process which leads to corneal angiogenesis in response to different injuries.

Excimer laser tissue interactions in the cornea.

Excimer lasers induces significant changes to corneal structure and corneal biomechanics. The aim of this paper is to describe all laser-tissue interactions which are relevant for clinical practice, particularly, we will focus on laser ablations profiles, causes of regression and haze and prevention of those. At last the manuscript will describe the impact on corneal biomechanics of different Laser Vision Corrections techniques.

Long term observation of ocular surface alkali burn in rabbit models: Quantitative analysis of corneal haze, vascularity and self-recovery.

Limbal Stem Cell Deficiency (LSCD), caused due to corneal injury, primarily by chemical/alkali burns, leads to compromised vision. Recently, several animal models of corneal alkali burn injury have become available. The majority of the studies with these animal models start interventions soon after the injury. However, in the clinical setting, there is a considerable delay before the intervention is initiated. Detailed knowledge of the molecular, histopathological, and clinical parameters associated with the progression of the injury leading to LSCD is highly desirable. In this context, we set out to investigate clinical, histopathological parameters of ocular surface alkali burn over a long period of time, post-injury. Limbal stem cell-deficient animal models of rabbits were created by alkali burn using sodium hydroxide, which was then assessed for their progression towards LSCD by grading the alkali burn, corneal haze, and vascularization. Additionally, cells present on the corneal surface after the burn was investigated by histology and immunophenotyping. Grading of rabbit eyes post-alkali burn had shown complete conjunctivalization in 80% (n = 12/15) of the rabbits with the alkali burn grade score of 3.88 ± 0.29 in three months and remained stable at four months (4.12 ± 0.24). However, ocular surface showed self-healing in 20% (n = 3/15) of the rabbits with a score of 1.67 ± 0.34 in four months irrespective of similar alkali injury. These self-healing corneas exhibited decreased opacity score from 2.51 ± 0.39 to 0.66 ± 0.22 (p = 0.002) and regressed vascularity from 1.66 ± 0.41 to 0.66 ± 0.33 in one to nine months, respectively. Restoration of the corneal phenotype (CK3+) was observed in central and mid-peripheral regions of the self-healing corneas, and histology revealed the localization of inflammatory cells to the peripheral cornea when compared to conjunctivalized and scarred LSCD eyes. Our study shows the essentiality to consider the time required for surgical intervention after the corneal alkali injury in rabbit models as evident from their tendency to self-heal and restore corneal phenotype without therapy. Such information on the possibility of self-healing should be useful in further studies as well as determining interventional timings and strategy during clinical presentation of corneal alkali burns.

Study on patterned photodynamic cross-linking for keratoconus.

PURPOSE: This study examined the patterned treatment of corneal collagen cross-linking (CXL) for keratoconus to reduce the complications caused by ultraviolet (UV) irradiation. By modifying the method of UV irradiation during the cross-linking process, cross-linking with a special structure is achieved, and the cross-linking effect is analyzed and compared to that of traditional cross-linking. By constructing an animal model of keratoconus, the process and effect of corneal cross-linking can be investigated more fundamentally. These studies provide valuable references for future cross-linking precision improvement and specialization. METHOD: By injecting exogenous collagenase into the corneal stroma of rabbits, the balance between collagenase and collagenase inhibitor in the corneal stroma was disrupted, the collagen fiber structure of the cornea was broken to simulate the pathogenesis of keratoconus, and an animal model of keratoconus was thus constructed. Two custom cross-linking patterns were designed with reference to the cable dome structure, and these two special patterns were irradiated and cross-linked by a DMD chip. The cross-linking effect was evaluated by optical coherence tomography (OCT), corneal topography and corneal biaxial tensile tests. The experimental rabbits were divided into four groups: group A, cross-linking of the bird's nest structure; group B, cross-linking of the honeycomb structure; group C, cross-linking of the traditional spot structure; and group D, normal (without modeling and cross-linking). RESULT: Following collagenase treatment, the collagen fiber structure of the rabbit cornea was destroyed, the central thickness of the cornea was reduced, the mechanical properties of the cornea were weakened, and no keratitis, ulcers or haze occurred. After the three cross-linking treatments, the morphology of the cornea improved, the density of the stromal layer increased, and the mechanical properties were enhanced. For the improvement of keratoconus mechanical properties, the average relative difference (Δ) of the four outcome measures was 61.98% for bird's nest cross-linking versus keratoconus (Wilcoxon rank sum test, P = 0.024), 16.13% for honeycomb cross-linking versus keratoconus (Wilcoxon rank sum test, P = 0.025), and 21.07% for traditional spot cross-linking versus keratoconus (Wilcoxon rank sum test, P = 0.014). All these differences are statistically significant. CONCLUSION: All three methods of cross-linking can improve the morphology and tissue structure of keratoconus and significantly improve the biomechanical properties of the cornea. Among them, the corneal cross-linking of the bird's nest structure attains the best biomechanical properties, followed by the corneal cross-linking of the traditional spot structure and of the honeycomb structure. This suggests that similar or better cross-linking effects can be achieved by designing custom structures with less UV exposure. This provides a direction for future research on better and more accurate pattern cross-linking treatments.

EFFECT OF PANRETINAL PHOTOCOAGULATION ON CORNEAL SENSATION AND TEAR FUNCTION IN PATIENTS WITH DIABETIC RETINOPATHY.

PURPOSE: To evaluate the early effects of panretinal photocoagulation (PRP) on corneal sensation and dry eye signs in patients with diabetic retinopathy. METHODS: Fifty patients with Type 2 diabetes mellitus and very severe nonproliferative or non-high-risk proliferative diabetic retinopathy who required PRP for the treatment of their retinal condition were enrolled. All patients were treated using a pattern PRP device. Esthesiometry, tear breakup time test, Schirmer test, and corneal staining pattern were evaluated at baseline and 2 months after the last session of PRP. RESULTS: Data from 88 eyes of 50 patients (41 right eyes and 47 left eyes) were analyzed. The mean tear breakup time test (right eyes) was decreased from 9.51 at baseline to 7.66 seconds after PRP (P < 0.001). The post-PRP eyes showed more advanced grades of corneal staining than pre-PRP assessment (P < 0.001). The average value of Schirmer test was 14.39 versus 12.29 mm (without anesthesia; P < 0.001) and 8.17 versus 7.15 mm (with anesthesia, P < 0.001) for baseline versus post-PRP measurements, respectively. The corneal sensation also showed decrease after laser therapy (4.93 versus 4.31 cm; P < 0.001). CONCLUSION: This study demonstrates that decreased corneal sensation and signs of dry eye are more common immediately after PRP for diabetic retinopathy. These conditions should be discussed with the patient preoperatively and managed postoperatively.

Corneal Biomechanical Changes Caused by Acute Elevation of IOP in Eyes with and without Glaucoma.

SIGNIFICANCE: Although corneal biomechanical parameters are well linked with glaucoma, their clinical utility has not yet been fully elucidated. This study was designed to provide unique evidence about the dynamic nature of corneal biomechanical parameters and their potential prognostic ability for glaucoma. PURPOSE: This study aimed to evaluate the effect of acute intraocular pressure (IOP) elevation on corneal hysteresis (CH) and corneal resistance factor (CRF) and the associations of these biomechanical parameters with glaucomatous disease. METHODS: Subjects participating in a prospective, longitudinal glaucoma research study had CH and CRF measured before and during ophthalmodynamometry during visits in the years 2011 to 2012. All participants were diagnosed with primary open-angle glaucoma, ocular hypertension, glaucoma suspect, or normal eyes and had a minimum of 3 years of study participation with at least five reliable visual field (VF) tests. Changes in CH, CRF, and IOP induced by ophthalmodynamometry were compared between diagnostic groups and evaluated for relationships with existing and future glaucomatous VF loss. RESULTS: In 248 eyes of 248 subjects followed up for 7.7 ± 2.3 years, ophthalmodynamometry induced a mean IOP increase from 15.1 to 29.9 mmHg, causing a mean 34 ± 28% increase in CRF and 21 ± 25% decrease in CH. Magnitude of CH change did not differ between diagnostic groups or between eyes that did (n = 20) and did not (n = 95) develop new VF loss during the study period, nor was it related to rate of future VF progression. CONCLUSIONS: Ophthalmodynamometry-induced IOP elevation resulted in significant acute changes in CH and CRF in this study; this suggests accounting for IOP may be important in clinical interpretation of these parameters. However, because the degree of CH change was not related to glaucoma or its progression, acute changes in CH and CRF do not seem to have a prognostic value for glaucoma.

Effect of Laser-assisted Subepithelial Keratectomy with Mitomycin C on Corneal Optical Density Measured with Confocal Microscopy.

SIGNIFICANCE: The development of confocal microscopy allows one to obtain high-resolution corneal images like its optical density. Some studies have evaluated the optical density with Scheimpflug cameras in the early post-operative period after photorefractive keratectomy, but no studies have evaluated the long-term evolution of optical density after surface ablation when mitomycin C is used. PURPOSE: This work aimed to study the changes in corneal optical density measured with confocal microscopy in eyes treated with laser-assisted subepithelial keratectomy (LASEK) and intraoperative mitomycin C (MMC) to correct myopia. METHODS: A study of 24 consecutive myopic eyes that underwent LASEK with 0.02% MMC and a control group of 24 healthy nontreated eyes was performed. Optical density was measured using the images by the confocal microscopy of the Heidelberg Retina Tomograph II with the Rostock Cornea Module. An analysis of confocal microscopy images was performed using the ImageJ software to obtain the optical density, in gray-scale units (GSU). The optical density of the stromal bed was evaluated 3 months, 15 months, and 3 years after surgery and was compared with the optical density at the equivalent depth of the stroma in controls. RESULTS: The mean values of optical density for the LASEK group were 81.7 ± 9.7, 78.6 ± 11.7, and 73.6 ± 18.7 GSU at 3 months, 15 months, and 3 years, respectively, and it was 61.8 ± 8.2 GSU for the control group. A statistically higher optical density 3 and 15 months after LASEK with MMC was found compared with controls (P < .001). No significant difference was found in optical density at 3 years post-operatively. CONCLUSIONS: Our study suggests that, after LASEK with MMC, the anterior corneal stroma has a higher optical density at 3 and 15 months post-operatively, which gradually returns to normal values 3 years after surgery.

Estimating principal plane positions for ocular power calculations in children and adults.

PURPOSE: To develop an age-dependent model to estimate the positions of the ocular and lenticular principal planes (pps) for use in ocular and axial power calculations. METHODS: Ocular power of the eye (Peye ) and axial power (Pax ) were calculated based on previously published average data of the ocular biometry and refraction in newborn infants, children and adults, as well as the associated pp positions. Next, regressions of the pp positions were made as a function of the logarithm of age, which were subsequently used to estimate Peye and Pax . These regression-based estimates were compared with the original data for validation. Finally, this procedure was repeated using the Atchison myopic eye model to determine the influence of myopia on the regression estimates. RESULTS: In adults, the corneal pps almost coincide at 0.058 mm in front of the cornea. The first lenticular pp position relative to the corneal apex is described by the equation: 5.809 - 0.697·exp(-0.211·Age) (r2  = 0.96), and the second lenticular pp by 6.026 - 0.684·exp(-0.232·Age) (r2  = 0.95). The first ocular pp position relative to the corneal apex is at 0.293·exp(-0.232·Age) - 2.2·10-3 ·Age + 1.723 (r2  = 0.99) and the second ocular pp is located at 0.392·exp(-0.181·Age) - 2.4·10-3 ·Age + 2.093 (r2  = 0.99). Estimates of Peye and Pax derived from these regressions led to minor differences from the original values (0.00 ± 0.06D and 0.00 ± 0.10D, respectively). These errors were not affected by ocular refraction between -10D and 0D, with errors of + 0.12 ± 0.00D and -0.02 ± 0.05D for Peye and Pax , respectively. CONCLUSION: The proposed regression models of the pp positions are sufficiently accurate to estimate Peye and Pax reliably. Interestingly, although the adult lens undergoes considerable physiological changes, its pps remain fixed with respect to the corneal apex.

Dynamic corneal biomechanics in different cell layers: in keratoconus and normal eyes.

PURPOSE: This study aimed to determine the relationship between corneal cellular structures and biomechanical deformation parameters in keratoconic (KC) and healthy eyes. METHODS: In this prospective comparative study, 29 eyes of 29 KC patients were age- and gender-matched with 28 eyes of 28 healthy individuals using frequency matching. Corneal parameters examined included the density of basal epithelial cells, anterior keratocytes, posterior keratocytes and endothelial cells as assessed by in vivo corneal confocal microscopy (HRT III-RCM, Heidelberg Engineering, www.heidelbergengineering.com). Additionally, the coefficient of variation of endothelial cell size (CV) and the percentage of hexagonal endothelial cells (HEX%) were measured by specular microscopy (Konan NSP-9900, Konan Medical, www.konanmedical.com). Further, biomechanical deformation parameters were derived from Corvis Scheimpflug Technology (Corvis ST, Oculus, www.oculus.de). All cellular and biomechanical deformation parameters in KC and normal groups were compared, and the relationship between cellular and biomechanical parameters calculated. RESULTS: In the KC group, the highest concavity (HC) delta arc length and maximum delta arc length were associated with endothelial cell density (Beta = -0.39, p = 0.03 and Beta = -0.60, p Ë‚ 0.001, respectively). Furthermore, there was a significant association between HC deflection length and HEX% (Beta = -0.67, p = 0.001). In the normal group, HC delta arc length and HC deflection length were significantly associated with endothelial cell density (Beta = 0.46, p = 0.02; and Beta = -0.51, p = 0.01, respectively). HC time, HC deformation amplitude and applanation 1 delta arc length were associated with CV (Beta = 0.50, p = 0.01; Beta = 0.27, p = 0.009; and Beta = -0.57, p = 0.002, respectively). Applanation 1 and applanation 2 deformation amplitudes were associated with HEX% (Beta = -0.49, p = 0.005; and Beta = -0.46, p = 0.02). CONCLUSIONS: Biomechanical deformation parameters were significantly correlated with endothelial cell properties in both KC and normal groups, thereby indicating the importance of the integrity of endothelial cells to the biomechanical properties of both KC and normal corneas.

Selective permeability of mouse blood-aqueous barrier as determined by 15N-heavy isotope tracing and mass spectrometry.

The blood-aqueous barrier plays a key role in regulating aqueous humor homeostasis by selectively restricting passage of proteins into the eye. The kinetics of aqueous flow are traditionally measured using artificial markers; however, these marker molecules do not address the barrier's selective permeability to plasma proteins. Here we applied stable isotope labeling of all serum proteins with nitrogen-15 (15N) atoms. Following systemic injection of this "heavy" serum in mice, the 15N-to-endogenous nitrogen-14 (14N) ratio of each protein in aqueous was measured by mass spectrometry. By monitoring the kinetic changes in these ratios, we determined the permeability profiles of hundreds of serum proteins. Meanwhile, we subjected one of the eyes to neoangiogenic wound healing by inflicting injury to the corneal limbus and compared the 15N proteomes between the normal eyes and the recovering eyes at 2 weeks after injury. In the injured eye, we detected markedly enhanced permeability to inhibitory complement regulator proteins, such as Cfh, Cfhr, Cfb, Cfi, Cfd, and Vtn. Many of the proteins in this group are implicated in age-related macular degeneration associated with leakage of the blood-retinal barrier due to inflammation. To rule out the possibility that the observed leakage was due simply to physical damage of the blood vessels, we separately created a neovascularization model using an alkali burn of the avascular cornea. In this latter model, elevated levels of Cfh and Cfb were evident. These findings suggest that ocular neovascularization is associated with enhanced permeability to serum complement regulators.

Corneal Sensory Experience via Transient Receptor Potential Vanilloid 1 Accelerates the Maturation of Neonatal Tearing.

Tearing maturates rapidly after birth, and external environmental challenges play a key role in promoting lacrimal functional maturation. However, little is known about the facilitative factors underlying this developmental process or the potential of application of these factors to treat hypofunction of the lacrimal gland. In this study, eye opening and the subsequent ocular surface sensory experience, which is thought to be involved in postnatal maturation of lacrimal function, were investigated. Our results demonstrated that eye opening after birth is essential for the maturation of neonatal tearing. The maturation process of lacrimal function is dependent on the ocular surface sensory experience via transient receptor potential cation channel subfamily member 1 after birth. This study provides, for the first time, important evidence of the sensory experience of the ocular surface in relation to the maturation of functional tear secretion during the postnatal period.