Distribution of Posterior Corneal Astigmatism According to Axis Orientation of Anterior Corneal Astigmatism

Purpose

To investigate the distribution of posterior corneal astigmatism in eyes with with-the-rule (WTR) and against-the-rule (ATR) anterior corneal astigmatism.

Methods

We retrospectively examined six hundred eight eyes of 608 healthy subjects (275 men and 333 women; mean age ± standard deviation, 55.3 ± 20.2 years). The magnitude and axis orientation of anterior and posterior corneal astigmatism were determined with a rotating Scheimpflug system (Pentacam HR, Oculus) when we divided the subjects into WTR and ATR anterior corneal astigmatism groups.

Results

The mean magnitudes of anterior and posterior corneal astigmatism were 1.14 ± 0.76 diopters (D), and 0.37 ± 0.19 D, respectively. We found a significant correlation between the magnitudes of anterior and posterior corneal astigmatism (Pearson correlation coefficient r = 0.4739, P<0.001). In the WTR anterior astigmatism group, we found ATR astigmatism of the posterior corneal surface in 402 eyes (96.6%). In the ATR anterior astigmatism group, we found ATR posterior corneal astigmatism in 82 eyes (73.9%). Especially in eyes with ATR anterior corneal astigmatism of 1 D or more and 1.5 D or more, ATR posterior corneal astigmatism was found in 28 eyes (59.6%) and 9 eyes (42.9%), respectively.

Conclusions

WTR anterior astigmatism and ATR posterior astigmatism were found in approximately 68% and 91% of eyes, respectively. The magnitude and the axis orientation of posterior corneal astigmatism were not constant, especially in eyes having high ATR anterior corneal astigmatism, as is often the case in patients who have undergone toric IOL implantation.     

CORNEAL SURFACE PROPERTIES OF TWO MARINE MAMMAL SPECIES1

Compared to the anterior surface of the normal human cornea, all Tursiops showed pronounced random, local curvature changes typical of old keratitis and scarring. Comparable but less severe findings apply to Zalophus. These irregularities were superimposed on the mild regular astigmatism of the spoon-shaped Tursiops cornea (mean central power is 26.8 D, SD = 3.8, N = 82). All Zalophus corneas showed no reliable regular astigmatism (overall mean power is 21.7 D, SD = 4.4, N = 53) but exhibited a flat, circular region about 6.5 mm in diameter along the nasal aspect of the horizontal meridian. Refraction through this cornea1 region showed aerial emmetropia, which accounts for equivalent marine and aerial visual resolution in this species.     

Reversible Femtosecond Laser-Assisted Myopia Correction: A Non-Human Primate Study of Lenticule Re-Implantation after Refractive Lenticule Extraction

LASIK (laser-assisted in situ keratomileusis) is a common laser refractive procedure for myopia and astigmatism, involving permanent removal of anterior corneal stromal tissue by excimer ablation beneath a hinged flap. Correction of refractive error is achieved by the resulting change in the curvature of the cornea and is limited by central corneal thickness, as a thin residual stromal bed may result in biomechanical instability of the cornea. A recently developed alternative to LASIK called Refractive Lenticule Extraction (ReLEx) utilizes solely a femtosecond laser (FSL) to incise an intrastromal refractive lenticule (RL), which results in reshaping the corneal curvature and correcting the myopia and/or astigmatism. As the RL is extracted intact in the ReLEx, we hypothesized that it could be cryopreserved and re-implanted at a later date to restore corneal stromal volume, in the event of keratectasia, making ReLEx a potentially reversible procedure, unlike LASIK. In this study, we re-implanted cryopreserved RLs in a non-human primate model of ReLEx. Mild intrastromal haze, noted during the first 2 weeks after re-implantation, subsided after 8 weeks. Refractive parameters including corneal thickness, anterior curvature and refractive error indices were restored to near pre-operative values after the re-implantation. Immunohistochemistry revealed no myofibroblast formation or abnormal collagen type I expression after 8 weeks, and a significant attenuation of fibronectin and tenascin expression from week 8 to 16 after re-implantation. In addition, keratocyte re-population could be found along the implanted RL interfaces. Our findings suggest that RL cryopreservation and re-implantation after ReLEx appears feasible, suggesting the possibility of potential reversibility of the procedure, and possible future uses of RLs in treating other corneal disorders and refractive errors.     

A quantitative analysis of astigmatism induced by pterygium

An analytical model has been developed for the localized corneal deformation produced in the region of the head of a pterygia. Astigmatism results when this localized deformation enters the central region or optical zone of the cornea. The amount and direction of the pterygia-induced astigmatism may be predicted from the values of the corneal curvature within the optical zone. The analytical solution of Lur'e based on the Papkovich-Neuber theory was applied to the anatomical and mechanical conditions affecting the cornea and conjunctiva. The force exerted by the head of a pterygia was measured experimentally for the first time. This force is of the order of that produced by the extraocular muscles in primary gaze. Using this model it is possible to predict that 2.35 diopters of the pterygia-induced astigmatism would result from a pterygia exerting 5 g of force along a meridian passing through the center of the cornea, and whose head is located 2.38 millimeters from the optical center of the cornea of an eye having a 4 mm pupillary diameter.     

Corneal accommodation in chick and pigeon

Summary We have investigated the role of changes in corneal radius of curvature in effecting accommodation in the bird's eye. It was found that in natural accommodation (measured by IR photoretinoscopy) changes of corneal radius of curvature (measured by IR photokeratometry) play an important role in both the chick and the pigeon. In the adult pigeon the cornea is indeed responsible for the largest part of natural accommodation (up to approx. 9 D). In this animal the corneal diameter (as seen from the optical axis of the eye) decreases in accommodation which can be taken to explain the change of corneal radius of curvature. In the chicken, corneal accommodation is combined with other mechanisms (total accommodative range 15–17 D, corneal accommodation about 8 D). The chicken's cornea is aspherical within the pupil area leading to large measurement variation in photokeratometry if the Purkinje images are not symmetrical to the pupillary axis.Abbreviation IR infrared     

Genome-wide meta-analysis of five Asian cohorts identifies PDGFRA as a susceptibility locus for corneal astigmatism

Corneal astigmatism refers to refractive abnormalities and irregularities in the curvature of the cornea, and this interferes with light being accurately focused at a single point in the eye. This ametropic condition is highly prevalent, influences visual acuity, and is a highly heritable trait. There is currently a paucity of research in the genetic etiology of corneal astigmatism. Here we report the results from five genome-wide association studies of corneal astigmatism across three Asian populations, with an initial discovery set of 4,254 Chinese and Malay individuals consisting of 2,249 cases and 2,005 controls. Replication was obtained from three surveys comprising of 2,139 Indians, an additional 929 Chinese children, and an independent 397 Chinese family trios. Variants in PDGFRA on chromosome 4q12 (lead SNP: rs7677751, allelic odds ratio?=?1.26 (95% CI: 1.16-1.36), P(meta)?=?7.87×10(-9)) were identified to be significantly associated with corneal astigmatism, exhibiting consistent effect sizes across all five cohorts. This highlights the potential role of variants in PDGFRA in the genetic etiology of corneal astigmatism across diverse Asian populations.     

Q 值调整个体化准分子激光原位角膜磨镶术术后角膜

目的:观察Q值调整非球面切削与标准化LASIK术后不同角膜直径下的角膜的非球面变化来分析Q值引导个性化切削技术的临床效果。方法:前瞻性研究。随机选取2010年至2011年来我院就诊的准分子手术患者35例68眼,分别进行标准化LASIK(S组:17例34眼)和Q值调整个体化LASIK(Q组:18例34眼)矫治。术前2组各项指标均相似,差异无统计学意义。术前屈光度数分别为标准组球镜平均值为-4.76±2.02D(-1.5D～-9.75D),柱镜平均值为-0.71±0.7D(0～-2.5D)和Q值个体化组球镜平均值为-4.78±2.21D(-1.5～-9.5D),柱镜平均值为-0.84±0.55D(0～-2.5D)两组,对比两组非球面切削与标准化LASIK术后1个月不同角膜直径下的Q值及△Q。结果:两组术前Q10、Q15、Q20、Q25、Q30平均值分别为标准组:-0.12、-0.17、-0.20、-0.25、-0.30,Q值个体化组:-0.14、-0.19、-0.22、-0.27、-0.32.。术后一个月两组的△Q(△Q=Qpost-Qpre)△Q10、△Q15、△Q20、△Q25、△Q30分别为标准组:0.58、0.88、1.08、1.10、0.85,Q值个体化组,0.39、0.75、1.03、1.10、0.84。△Q10和△Q15术前术后变化在角膜直径为3.5mm之内时的差异有统计学意义。结论:Q值调整的个体化准分子激光原位角膜磨镶术术后角膜非球面变化与标准组相比皆由术前的长椭圆型Q值向扁椭圆型变化,但Q值调整的个体化组在角膜中央区的扁椭圆变化小于标准组,尤其在角膜中央3.5mm。说明Q值调整的个体化LASIK组在角膜中央区比标准组具有优势。     

Biomechanical modeling of refractive corneal surgery

The aim of refractive corneal surgery is to modify the curvature of the cornea to improve its dioptric properties. With that goal, the surgeon has to define the appropriate values of the surgical parameters in order to get the best clinical results, i.e., laser and geometric parameters such as depth and location of the incision, for each specific patient. A biomechanical study before surgery is therefore very convenient to assess quantitatively the effect of each parameter on the optical outcome. A mechanical model of the human cornea is here proposed and implemented under a finite element context to simulate the effects of some usual surgical procedures, such as photorefractive keratectomy (PRK), and limbal relaxing incisions (LRI). This model considers a nonlinear anisotropic hyperelastic behavior of the cornea that strongly depends on the physiological collagen fibril distribution. We evaluate the effect of the incision variables on the change of curvature of the cornea to correct myopia and astigmatism. The obtained results provided reasonable and useful information in the procedures analyzed. We can conclude from those results that this model reasonably approximates the corneal response to increasing pressure. We also show that tonometry measures of the IOP underpredicts its actual value after PRK or LASIK surgery.     

Evaluation of the Shape Symmetry of Bilateral Normal Corneas in a Chinese Population

Purpose

To investigate the bilateral symmetry of the global corneal topography in normal corneas with a wide range of curvature, astigmatism and thickness values

Design

Cross-Sectional Study

Methods

Topography images were recorded for the anterior and posterior surfaces of 342 participants using a Pentacam. Elevation data were fitted to a general quadratic model that considered both translational and rotational displacements. Comparisons between fellow corneas of estimates of corneal shape parameters (elevation, radius in two main directions, R_x and R_y, and corresponding shape factors, Q_x and Q_y) and corneal position parameters (translational displacements: x₀, y₀ and z₀, and rotational displacements: α, β and γ) were statistically analyzed.

Results

The general quadratic model provided average RMS of fit errors with the topography data of 1.7±0.6 µm and 5.7±1.3 µm in anterior and posterior corneal surfaces. The comparisons showed highly significant bilateral correlations with the differences between fellow corneas in R_x, R_y, Q_x and Q_y of anterior and posterior surfaces remaining insignificantly different from zero. Bilateral differences in elevation measurements at randomly-selected points in both corneal central and peripheral areas indicated strong mirror symmetry between fellow corneas. The mean geometric center (x₀, y₀, z₀) of both right and left corneas was located on the temporal side and inferior-temporal side of the apex in anterior and posterior topography map, respectively. Rotational displacement angle α along X axis had similar distributions in bilateral corneas, while rotation angle β along Y axis showed both eyes tilting towards the nasal side. Further, rotation angle γ along Z axis, which is related to corneal astigmatism, showed clear mirror symmetry.

Conclusions

Analysis of corneal topography demonstrated strong and statistically-significant mirror symmetry between bilateral corneas. This characteristic could help in detection of pathological abnormalities, disease diagnosis, measurement validation and surgery planning.     

The corneal surface of aquatic vertebrates: microstructures with optical and nutritional function?

The anterior surface of the mammalian cornea plays an important role in maintaining a smooth optical interface and consequently a sharp retinal image. The smooth surface is produced by a tear film, which adheres to a variety of microprojections, which increase the cell surface area, improve the absorbance of oxygen and nutrients and aid in the movement of metabolic products across the outer cell membrane. However, little is known of the structural adaptations and tear film support provided in other vertebrates from different environments. Using field emission scanning electron microscopy; this study examines the density and surface structure of corneal epithelial cells in representative species of the classes Cephalaspidomorphi, Chondrichthyes, Osteichthyes, Amphibia, Reptilia, Aves and Mammalia, including some Marsupialia. Variations in cell density and the structure and occurrence of microholes, microridges, microplicae and microvilli are described with respect to the demands placed upon the cornea in different aquatic environments such as marine and freshwater. A progressive decrease in epithelial cell density occurs from marine (e.g. 29348 cells mm(-2) in the Dover sole Microstomius pacficus) to estuarine or freshwater (e.g. 5999 cells mm(-2) in the black bream Acanthopagrus butcheri) to terrestrial (e.g. 2126 cells mm(-2) in the Australian koala Phascolarctos cinereus) vertebrates, indicating the reduction in osmotic stress across the corneal surface. The microholes found in the Southern Hemisphere lampreys, namely the pouched lamprey (Geotria australis) and the shorthead lamprey (Mordacia mordax) represent openings for the release of mucus, which may protect the cornea from abrasion during their burrowing phase. Characteristic of marine teleosts, fingerprint-like patterns of corneal microridges are a ubiquitous feature, covering many types of sensory epithelia (including the olfactory epithelium and the oral mucosa). Like microplicae and microvilli, microridges stabilize the tear film to maintain a smooth optical surface and increase the surface area of the epithelium, assisting in diffusion and active transport. The clear interspecific differences in corneal surface structure suggest an adaptive plasticity in the composition and stabilization of the corneal tear film in various aquatic environments.     

Patient-specific modeling of corneal refractive surgery outcomes and inverse estimation of elastic property changes

The purpose of this study is to develop a 3D patient-specific finite element model (FEM) of the cornea and sclera to compare predicted and in vivo refractive outcomes and to estimate the corneal elastic property changes associated with each procedure. Both eyes of a patient who underwent laser-assisted in situ keratomileusis (LASIK) for myopic astigmatism were modeled. Pre- and postoperative Scheimpflug anterior and posterior corneal elevation maps were imported into a 3D corneo-scleral FEM with an unrestrained limbus. Preoperative corneal hyperelastic properties were chosen to account for meridional anisotropy. Inverse FEM was used to determine the undeformed corneal state that produced <0.1% error in anterior elevation between simulated and in vivo preoperative geometries. Case-specific 3D aspheric ablation profiles were simulated, and corneal topography and spherical aberration were compared at clinical intraocular pressure. The magnitude of elastic weakening of the residual corneal bed required to maximize the agreement with clinical axial power was calculated and compared with the changes in ocular response analyzer (ORA) measurements. The models produced curvature maps and spherical aberrations equivalent to in vivo measurements. For the preoperative property values used in this study, predicted elastic weakening with LASIK was as high as 55% for a radially uniform model of residual corneal weakening and 65% at the point of maximum ablation in a spatially varying model of weakening. Reductions in ORA variables were also observed. A patient-specific FEM of corneal refractive surgery is presented, which allows the estimation of surgically induced changes in corneal elastic properties. Significant elastic weakening after LASIK was required to replicate clinical topographic outcomes in this two-eye pilot study.     

Geometrical Custom Modeling of Human Cornea In Vivo and Its Use for the Diagnosis of Corneal Ectasia

Aim

To establish a new procedure for 3D geometric reconstruction of the human cornea to obtain a solid model that represents a personalized and in vivo morphology of both the anterior and posterior corneal surfaces. This model is later analyzed to obtain geometric variables enabling the characterization of the corneal geometry and establishing a new clinical diagnostic criterion in order to distinguish between healthy corneas and corneas with keratoconus.

Method

The method for the geometric reconstruction of the cornea consists of the following steps: capture and preprocessing of the spatial point clouds provided by the Sirius topographer that represent both anterior and posterior corneal surfaces, reconstruction of the corneal geometric surfaces and generation of the solid model. Later, geometric variables are extracted from the model obtained and statistically analyzed to detect deformations of the cornea.

Results

The variables that achieved the best results in the diagnosis of keratoconus were anterior corneal surface area (ROC area: 0.847, p<0.000, std. error: 0.038, 95% CI: 0.777 to 0.925), posterior corneal surface area (ROC area: 0.807, p<0.000, std. error: 0.042, 95% CI: 0,726 to 0,889), anterior apex deviation (ROC area: 0.735, p<0.000, std. error: 0.053, 95% CI: 0.630 to 0.840) and posterior apex deviation (ROC area: 0.891, p<0.000, std. error: 0.039, 95% CI: 0.8146 to 0.9672).

Conclusion

Geometric modeling enables accurate characterization of the human cornea. Also, from a clinical point of view, the procedure described has established a new approach for the study of eye-related diseases.     

Effects of Optically Imposed Astigmatism on Early Eye Growth in Chicks

PurposeTo determine the effects of optically imposed astigmatism on early eye growth in chicks.Methods5-day-old (P5) White Leghorn chicks were randomly assigned to either wear, monocularly, a “high magnitude” (H: +4.00DS/-8.00DC) crossed-cylindrical lens oriented at one of four axes (45, 90, 135, and 180; n = 20 in each group), or were left untreated (controls; n = 8). Two additional groups wore a “low magnitude” (L: +2.00DS/−4.00DC) cylindrical lens orientated at either axis 90 or 180 (n = 20 and n = 18, respectively). Refractions were measured at P5 and after 7 days of treatment for all chicks (P12), whereas videokeratography and ex-vivo eyeshape analysis were performed at P12 for a subset of chicks in each group (n = 8).ResultsCompared to controls, chicks in the treatment groups developed significant amounts of refractive astigmatism (controls: 0.03±0.22DC; treatment groups: 1.34±0.22DC to 5.51±0.26DC, one-way ANOVAs, p≤0.05) with axes compensatory to those imposed by the cylindrical lenses. H cylindrical lenses induced more refractive astigmatism than L lenses (H90 vs. L90: 5.51±0.26D vs. 4.10±0.16D; H180 vs. L180: 2.84±0.44D vs. 1.34±0.22D, unpaired two-sample t-tests, both p≤0.01); and imposing with-the-rule (H90 and L90) and against-the-rule astigmatisms (H180 and L180) resulted in, respectively, steeper and flatter corneal shape. Both corneal and internal astigmatisms were moderately to strongly correlated with refractive astigmatisms (Pearson’s r: +0.61 to +0.94, all p≤0.001). In addition, the characteristics of astigmatism were significantly correlated with multiple eyeshape parameters at the posterior segments (Pearson’s r: -0.27 to +0.45, all p≤0.05).ConclusionsChicks showed compensatory ocular changes in response to the astigmatic magnitudes imposed in this study. The correlations of changes in refractive, corneal, and posterior eyeshape indicate the involvement of anterior and posterior ocular segments during the development of astigmatism.     

透明角膜切口白内障术后角膜曲率的临床观察*

目的:观察年龄相关性白内障行透明角膜切口超声乳化吸除及人工晶体植入术后角膜曲率的变化及相对稳定的时间。方法:收集2016年6月-8月在哈尔滨医科大学附属第一医院伍连德纪念医院进行的3.0 mm透明角膜切口白内障超声乳化吸除及人工晶体植入术的患者200例216眼,其中男88例、女128例,平均年龄71.2岁,进行相应的术前检查,并检查术前、术后第一天、一周、一个月、和三个月时的角膜曲率、视力、眼压并行相应的统计学分析。结果:术后不同时间点视力0.5的恢复情况:第一天为147眼(68.05%)、一周为175眼(81.02%)、一个月为193眼(89.35%)、三个月为197眼(91.20%);术前角膜曲率为43.94±1.35、术后第一天、术后一周的角膜曲率分别为44.98±1.06、44.45±1.18,与术前相比有显著性差异(p0.05),术后一个月、三个月的角膜曲率分别为44.13±1.27、44.02±1.24,与术前相比无显著性差异(p0.05);术源性散光于术后一天达到最大,随后逐渐减小,术后一个月、三个月与术后一天比较有显著性差异(p0.05),术后三个月与一个月比较无显著性差异(p0.05),术源性散光术后逐渐下降,并于一个月时趋于稳定。结论:3.0 mm透明角膜切口白内障超声乳化吸除及人工晶体植入术患者在术后一个月的角膜曲率基本稳定,恢复至术前状态,屈光状态趋于稳定,术源性角膜散光较小,术后视力恢复至较好状态。     

X-ray scattering used to map the preferred collagen orientation in the human cornea and limbus

Many properties of connective tissues are governed by the organization of the constituent collagen. For example, the organization of collagen in the cornea and the limbus, where the cornea and sclera meet, is an important determinant of corneal curvature and hence of the eye's focusing power. We have used synchrotron X-ray scattering to map the orientation of the collagen fibrils throughout the human cornea, limbus, and adjacent sclera. We demonstrate a preferred orientation of collagen in the vertical and horizontal directions that is maintained to within about 1 mm from the limbus, where a circular or tangential disposition of fibrils occurs. The data are also used to map the relative distribution of both the total and the preferentially aligned collagen in different parts of the tissue, revealing considerable anisotropy. The detailed structural information provided is an important step toward understanding the shape and the mechanical properties of the tissue.     

OCT layered tomography of the cornea provides new insights on remodeling after photorefractive keratectomy

OCT (optical coherence tomography) of corneal layers was generated to analyze the remodeling of the epithelium and stroma after photorefractive keratectomy (PRK). Myopic PRK was performed in 15 patients. One eye underwent manual scraping of epithelium while the other was treated with Epi clear. Epi clear allowed a gentler removal of the epithelium compared to manual scraping. Scheimpflug (Pentacam, OCULUS Optikgerate Gmbh, Wetzlar, Germany) and OCT (RTVue, Optovue Inc., Fremont, California, USA) scans of the cornea were performed before and after PRK (3 months). The OCT scanner and Pentacam acquired 8 and 25 radial 2‐D scans of the cornea, respectively. The results showed similar topographic changes on the anterior corneal surface between Scheimpflug and OCT imaging. The curvature of the underlying anterior surface of the stroma after PRK was similar to the anterior corneal surface (air‐epithelium interface), when measured with OCT. Aberrometric changes were mostly similar between Scheimpflug and OCT. However, Scheimpflug imaging reported greater changes in spherical aberration and corneal higher order aberrations than OCT after PRK. This is the first study to quantify the curvatures of the stromal layers with OCT after PRK. New insights were gained, which could be useful for refinement of surgical ablation algorithms, refractive procedures and detection of ectasia.      

Effect of Orbital Decompression on Corneal Topography in Patients with Thyroid Ophthalmopathy

Objective

To evaluate changes in corneal astigmatism in patients undergoing orbital decompression surgery.

Methods

This retrospective, non randomized comparative study involved 42 eyes from 21 patients with thyroid ophthalmopathy who underwent orbital decompression surgery between September 2011 and September 2014. The 42 eyes were divided into three groups: control (9 eyes), two-wall decompression (25 eyes), and three-wall decompression (8 eyes). The control group was defined as the contralateral eyes of nine patients who underwent orbital decompression surgery in only one eye. Corneal topography (Orbscan II), Hertel exophthalmometry, and intraocular pressure were measured at 1 month before and 3 months after surgery. Corneal topographic parameters analyzed were total astigmatism (TA), steepest axis (SA), central corneal thickness (CCT), and anterior chamber depth (ACD).

Results

Exophthalmometry values and intraocular pressure decreased significantly after the decompression surgery. The change (absolute value (|x|) of the difference) in astigmatism at the 3 mm zone was significantly different between the decompression group and the controls (p = 0.025). There was also a significant change in the steepest axis at the 3 mm zone between the decompression group and the controls (p = 0.033). An analysis of relevant changes in astigmatism showed that there was a dominant tendency for incyclotorsion of the steepest axis in eyes that underwent decompression surgery. Using Astig PLOT, the mean surgically induced astigmatism (SIA) was 0.21±0.88 D with an axis of 46±22°, suggesting that decompression surgery did change the corneal shape and induced incyclotorsion of the steepest axis.

Conclusions

There was a significant change in corneal astigmatism after orbital decompression surgery and this change was sufficient to affect the optical function of the cornea. Surgeons and patients should be aware of these changes.     

Radius of the curvature of the femur in the sagittal plane

The degree of anterior curvature was measured on 30 cadaveric human femora, of unknown age and sex, by a spherometer. The mean anterior curvature radius was (1381.28 +/- 118.63) mm with a considerable interspecimen variation, the maximal value was 3262.66 mm and the minimal 695.54 mm.     

In search of markers for the stem cells of the corneal epithelium

The anterior one-fifth of the human eye is called the cornea. It consists of several specialized cell types that work together to give the cornea its unique optical properties. As a result of its smooth surface and clarity, light entering the cornea focuses on the neural retina allowing images to come into focus in the optical centres of the brain. When the cornea is not smooth or clear, vision is impaired. The surface of the cornea consists of a stratified squamous epithelium that must be continuously renewed. The cells that make up this outer covering come from an adult stem cell population located at the corneal periphery at a site called the corneal limbus. While engaging in the search for surface markers for corneal epithelial stem cells, vision scientists have obtained a better understanding of the healthy ocular surface. In this review, we summarize the current state of knowledge of the ocular surface and its adult stem cells, and analyse data as they now exist regarding putative corneal epithelial stem cell markers.     

Keratocan-deficient mice display alterations in corneal structure

Keratocan (Kera) is a cornea-specific keratan sulfate proteoglycan (KSPG) in the adult vertebrate eye. It belongs to the small leucine-rich proteoglycan (SLRP) gene family and is one of the major components of extracellular KSPG in the vertebrate corneal stroma. The Kera gene is expressed in ocular surface tissues including cornea and eyelids during morphogenesis. Corneal KSPGs play a pivotal role in matrix assembly, which is accountable for corneal transparency. In humans, mutations of the KERA gene are associated with cornea plana (CNA2) that manifests decreases in vision acuity due to the flattened forward convex curvature of cornea. To investigate the biological role of the Kera gene and to establish an animal model for corneal plana, we generated Kera knockout mice via gene targeting. Northern and Western blotting and immunohistochemical analysis showed that no Kera mRNA or keratocan protein was detected in the Kera-/- cornea. The expression levels of other SLRP members including lumican, decorin, and fibromodulin were not altered in the Kera-/- cornea as compared with that of the wild-type littermates. Mice lacking keratocan have normal corneal transparency at the age of 12 months. However, they have a thinner corneal stroma and a narrower cornea-iris angle of the anterior segment in comparison to the wild-type littermates. As demonstrated by transmission electron microscopy, Kera-/- mice have larger stromal fibril diameters and less organized packing of collagen fibrils in stroma than those of wild type. Taken together, our results showed that ablation of the Kera gene resulted in subtle structural alterations of collagenous matrix and did not perturb the expression of other SLRPs in cornea. Keratocan thus plays a unique role in maintaining the appropriate corneal shape to ensure normal vision.