Proliferative and migratory aptitude in pterygium

Pterygium is a chronic fibrovascular overgrowth on the corneal surface and is often associated with inflammation, astigmatism and obstructed vision. The common treatment is surgical removal but post-operative recurrences with more aggressive behavior are common. However, there is a controversy in the pathogenesis of primary pterygium between limbal stem cell failure versus proliferation. In this study, we explore the proliferative and migratory aptitude in pterygium by characterizing the growth and migration pattern of pterygial cells in the head (on the cornea), the neck (over the focal limbus), and the body (on the conjunctiva) epithelia of 12 full-length primary pterygia. Immunofluorescence and quantification analyses showed a spatial expression pattern of markers for stem cells, cell growth, and matrix metalloproteinases. Beside the basal epithelia in all three regions, p63α^strong cells were located in suprabasal layers in head, weak in the body and absent in neck. Pertinent cell proliferation in head than body epithelia was revealed by its higher colony-forming efficiency. ATP-binding cassette transporter glycoprotein family member-2 and cytokeratin-15 were found mainly in the body basal epithelia, similar to that in normal conjunctiva. Much fewer proliferating stem-like cells in the neck region supported the limbal failure as a cause of pterygium formation. Pax6, matrix metalloproteinase-2 and -9 were more expressed in the head than in the other two regions. Our results indicate the importance of pterygium head in tissue growth and invasion and its likely involvement in post-operation recurrence.     

Quantification of biomechanical properties of human corneal scar using acoustic radiation force optical coherence elastography

Biomechanical properties of corneal scar are strongly correlated with many corneal diseases and some types of corneal surgery, however, there is no elasticity information available about corneal scar to date. Here, we proposed an acoustic radiation force optical coherence elastography system to evaluate corneal scar elasticity. Elasticity quantification was first conducted on ex vivo rabbit corneas, and the results validate the efficacy of our system. Then, experiments were performed on an ex vivo human scarred cornea, where the structural features, the elastic wave propagations, and the corresponding Young’s modulus of both the scarred region and the normal region were achieved and based on this, 2D spatial distribution of Young’s modulus of the scarred cornea was depicted. Up to our knowledge, we realized the first elasticity quantification of corneal scar, which may provide a potent tool to promote clinical research on the disorders and surgery of the cornea.     

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.     

Low-dose strontium-90 irradiation is effective in preventing the recurrence of pterygia: a ten-year study

Background

To study the long-term effects of low-dosage strontium-90 (Sr90) irradiation on the recurrence of pterygium.

Methodology/Principal Findings

One hundred twenty eyes from 104 patients with primary or recurrent pterygia were treated with surgery followed by Sr90 irradiation. In brief, starting on the sixth day after surgery, patients were treated with irradiation three times every other day at a total combined dosage of 2000 cGy to 3000 cGy. Corneal topography was used to evaluate ocular surface regularity before and after treatment. Patient follow-up was performed 2 days, 5 days, 2 weeks, 1 month, 3 months, 1 year, 5 years, and 10 years after surgery. Recurrence of pterygium was not observed in any of the patients in this study. Obvious cataract progression was observed in 6 eyes, which may be due to aging. During follow-up studies, only one eye was reported with dryness and foreign-body sensation. Significant pterygium-induced astigmatism was observed in corneal topography, which decreased after surgery.

Conclusions/Significance

Sr90 irradiation is effective in preventing the recurrence of primary and recurrent pterygia. We recommend delivering a total combined dosage of 2000 cGy to 3000 cGy of Sr90 irradiation administered in three batches every other day starting from the sixth day after surgery. Surgery is important in the rapid recovery of the cornea from pterygium-induced astigmatism.     

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.     

Calculation and application of the anterior surface area of a model human cornea

The macroscopic anterior surface area was calculated for three models of the average human cornea. Two models, a general ellipsoid and a rotational ellipse (rotationally symmetric ellipsoid) gave a surface area of 132 mm2, while a spherical model gave 126 mm2. A general ellipsoidal model having the maximum radius horizontal (with-the-rule corneal astigmatism) has less surface area than a rotational ellipse with the same horizontal radius. For a corneal sagittal height of 2.59 mm, the surface area of an ellipsoidal cornea equals -19.2Q + 16.3R -0.476 which specifies a rotational ellipse (radius R, asphericity Q) of equal surface area. In a cornea with the maximum radius vertical (against-the-rule corneal astigmatism), the ellipsoid has slightly more surface area than a rotational ellipse with the same horizontal radius of curvature. For a given horizontal radius of curvature, the sphere has the lowest surface area. For a corneal sagittal height s of 2.59 mm, the sphere underestimates by 8% the surface area of a rotational ellipse with asphericity -0.5. The anterior corneal surface area of a rotational ellipse model, radius R, asphericity Q is given by 2 pi Rs- 19.2Q. In all three models, the surface area increases with horizontal radius of curvature. In the rotational ellipse model, the rate of increase (slope) is independent of asphericity, and the slope found in with-the-rule astigmatism is less than the slope found with against-the-rule astigmatism. The calculated surface area predicts a precorneal tear volume of 0.86 microliter for a 6.5 micron tear thickness. The apparent, or plane projected are of an epithelial lesion underestimates the curved surface area with a percentage error that increases rapidly with lesion diameter. For a 12 mm diameter lesion on a rotational ellipse model, the apparent area underestimates the surface area by 18%. The average posterior corneal surface in human is not spherical but imitates the anterior surface, and has an area of 137 mm2 or 3.8% greater than the anterior area.     

The eye of the hooded seal,Cystophora cristata,in air and water

Summary Multiple refractive state measurements were made on a male and female hooded seal (Cystophora cristata) when the eyes were exposed to air and to water. The measures, made by conventional retinoscopy and by photorefraction, show that the seals are moderately hyperopic (2–3 diopters) in water and moderately myopic (2–4 diopters) in air. No significant astigmatism was noted in either medium. The absence of refractive state variation over time suggests that an accommodative mechanism is insignificant or absent, although histological study indicates that the ciliary muscle is well developed.Photokeratoscopy, carried out on two animals with two keratoscopic instruments, show that the cornea is relatively flat (30 mm, or about one-half the diameter of the eye). Furthermore the cornea is only slightly astigmatic (less than 1 diopter). The refractive power of the external corneal surface (in air), calculated from a measurement of corneal refractive index of 1.378, amounts to only 10 or 11 diopters.As in the typical fish eye, hooded seal lenses are spherical or nearly spherical in shape (24–23 mm), and have short focal lengths (30–32 mm). Focal measures for rays at varying distances from the lens center indicate that spherical aberration is well corrected.There is no indication in this seal species, of a previously reported adaptation involving a highly astigmatic cornea which together with a slit pupil can minimize the optical effect of movement from water to air.     

Fine structure of the dioptric apparatus in the stalk eye of Onchidium verruculatum (Gastropoda, Stylommatophora): a distinct lamellar substructure of the lens

 The dioptric apparatus of the stalk eye in Onchidium verruculatum, including a tentacular epidermis, a cornea, and a lens, was examined using transmission electron microscopy. The tentacular epidermis was formed by columnar epidermal cells, sensory dendrites, and glandular cells. The cornea was an anterior part of the eye vesicle and consisted of corneal cells which contained abundant glycogen particles but no dark pigment granules in their cytoplasm. An acellular, transparent, ellipsoidal lens was located in the center of the eye vesicle. The lens showed a marginal zone, an outer zone, a transitional zone, an inner zone, and a central region arranged concentrically. The outer zone was the most intense electron-dense region and was finely granular in structure. The marginal zone was also finely granular and surrounded the outer zone with many hair-like slender strands on the retinal side. Toward the center of the lens this homogeneous fine granularity gradually changed into globular or rod-like substructures, about 30 nm in diameter, and then abruptly transformed into a lamellar substructure of about 30 nm in thickness. The inner zone contained a mosaic of lamellar substructures which were arranged in a fingerprint pattern that was particularly enhanced with periodic acid methenamine silver proteinate staining. The center itself consisted of deformed lamellar substructures. The concentric arrangement of substructures inside the lens of the O. ver-ruculatum stalk eye is probably responsible for the concentration and/or refraction of light. Accepted: 5 December 1997     

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.     

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.     

Fibronectin in the development of embryonic chick eye.

The time course of appearance and distribution of fibronectin in the developing eye have been studied in chick embryos by indirect immunofluorescence. At the 12-somite stage, fibronectin was detected as a layer under the ectodermal cells overlying the forebrain vesicle; it was also present in the head mesenchyme. During formation of the lens placode and its invagination, a zone containing fibronectin persisted around the lens as a component of the capsule. The fibronectin-containing layer was separated from the corneal epithelial cells during the formation of the acellular stroma. The migrating corneal endothelial cells were seen posterior to the fibronectin layer. The secondary stroma was strongly positive for fibronectin. Fibronectin disappeared from the cornea starting from its posterior part along with the corneal condensation. In the newborn chicken cornea, fibronectin was present only in Descemet's membrane. In addition, the embryonic vitreous body had a network of fibronectin-containing material. The distribution of fibronectin in the developing cornea, as well as other data available on this glycoprotein, is consistent with the proposed role of fibronectin in positioning and migration of cells and in organization of the extracellular matrix.     

Finite element simulation of arcuates for astigmatism correction

In order to simulate the corneal incisions used to correct astigmatism, a three-dimensional finite element model was generated from a simplified geometry of the anterior half of the ocular globe. A hyperelastic constitutive behavior was assumed for cornea, limbus and sclera, which are collagenous materials with a fiber structure. Due to the preferred orientations of the collagen fibrils, corneal and limbal tissues were considered anisotropic, whereas the sclera was simplified to an isotropic one assuming that fibrils are randomly disposed. The reference configuration, which includes the initial strain distribution that balances the intraocular pressure, is obtained by an iterative process. Then the incisions are simulated. The final positions of the nodes belonging to the incised meridian and to the perpendicular one are fitted by both radii of curvature, which are used to calculate the optical power. The simulated incisions were those specified by Lindstrom's nomogram [Chu, Y., Hardten, D., Lindquist, T., Lindstrom, R., 2005. Astigmatic keratotomy. Duane's Ophthalmology. Lippincott Williams and Wilkins, Philadelphia] to achieve 1.5, 2.25, 3.0, 4.5 and 6.0D of astigmatic change, using the next values for the parameters: length of 45 degrees , 60 degrees and 90 degrees , an optical zone of 6mm, single or paired incisions. The model gives results similar to those in Lindstrom's nomogram [Chu et al., 2005] and can be considered a useful tool to plan and simulate refractive surgery by predicting the outcomes of different sorts of incisions and to optimize the values for the parameters involved: depth, length, position.     

The Effect of Spatial Inhomogeneity of the Cornea on the Deformation Properties of the Eyeball and the Results of Maklakoff Applanation Tonometry

A two-component model of the eyeball that represents the cornea as a momentless, linearly elastic deformable surface and the scleral region, as an elastic element that responds to intraocular pressure changes by volume changes, has been used to analyze the effect of spatial inhomogeneity in the distribution of effective corneal stiffness on the mechanical properties of the eye. The effective stiffness of the cornea characterized both the elastic properties and the thickness of the cornea within the framework of the model. Various axisymmetric forms of the effective stiffness distribution characterized by monotonic increase along the arc between a point on the corneal surface and the apex of the cornea were studied. The considered distributions simulated both natural inhomogeneity and apical region weakening due to surgical interventions. Numerical simulation yielded the dependences of deformation parameters on intraocular pressure changes. These parameters characterized the deformation properties of both the cornea (apex displacement) and the eyeball as a whole (intraocular volume change). In the case of moderate inhomogeneity, the dependences were only slightly different from those for a homogeneous cornea with an effective stiffness equal to the mean value for the corresponding inhomogeneous distribution. A noticeable increase in the integral response of the cornea and the eyeball as a whole to changes in pressure was observed if the effective stiffness amplitude was very high (two or more times higher than the mean value). The effect of inhomogeneity on the results of tonometric measurements with a Maklakoff tonometer (flat stamp) was studied. The tonometric difference, that is, the difference between the tonometric pressure (in the loaded eye) and the true pressure (before loading), mainly depended on the average stiffness of the cornea in this case as well, with a substantial increase observed at very high stiffness amplitudes only. Apical weakening of the cornea led to an increase (although not very pronounced) of the tonometric difference.     

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.     

The corneal epithelial stem cell

The aim of this paper was to develop a GFP-expressing transgenic mouse model for the keratoepithelioplasty and to use this to follow the outcome of this form of graft, when placed on an inflamed corneal surface. Further aims were to characterize both the graft and the epithelial surface of the mouse and rat cornea using putative stem cell markers (P63 and Telomerase) and marker of cell differentiation (14-3-3 sigma). Keratepithelioplasty was carried out using a GFP transgenic mouse cornea as donor tissue. Fluorescent epithelial outgrowth from each keratepithelioplasty was scored and quantified. Donor corneal graft tissue was obtained from the paracentral region or the anatomical limbal region of murine corneas. Paracentral donor grafts (n = 20) consistently demonstrated a significant increase in proliferative potential compared to grafts obtained from the anatomical limbal region of the mouse cornea (n = 25) (P = 0.000, Mann-Whitney U). Correspondingly, P63 expression was maximal in the paracentral region of the mouse cornea, in keeping with the demonstrated increased proliferative potential of donor grafts harvested from this region of the cornea. The murine corneal epithelium demonstrated decreased rather than increased cellular layers at the limbal region, in contrast to that of the rat or human epithelium. In addition, as a general finding in all species tested, there was an apparent increase noted in P63 expression in basal corneal epithelial cells in regions that had increased cellular layers (limbus in humans and rats and the paracentral corneal region in the mouse). Epithelium, which had migrated from donor grafts onto recipient corneas, retained P63 expression for the period of time examined (up to 3 days postengraftment). In addition, the conjunctival surface of an injured conjunctivalized displayed an abnormal pattern of P63 expression. Telomerase expression was widespread throughout many layers of both the murine and rat corneal epithelium. In the mouse and rat corneal epithelium P63 expression was maximal in areas of increased proliferative potential. Its expression, however, was not confined to stem cells alone. Migrating cells from transplanted keratoepithelial grafts retained P63 expression at least in the early stages post-transplantation. Finally, damaged conjunctivalized corneas displayed an abnormal P63 expression pattern when compared to either normal conjunctiva or normal cornea.     

An approach to localizing corneal pain representation in human primary somatosensory cortex

The cornea has been a focus of animal electrophysiological research for decades, but little is known regarding its cortical representation in the human brain. This study attempts to localize the somatotopic representation of the cornea to painful stimuli in human primary somatosensory cortex using functional magnetic resonance imaging (fMRI). In this case study, a subject was imaged at 3T while bright light was presented in a block-design, which either produced pain and blinking (during photophobia) or blinking alone (after recovery from photophobia). Pain and blinking produced precisely localized activations in primary somatosensory cortex and primary motor cortex. These results indicate that noxious stimulation of the cornea can produce somatotopic activation in primary somatosensory cortex. This finding opens future avenues of research to evaluate the relationship between corneal pain and central brain mechanisms relating to the development of chronic pain conditions, such as dry eye-like symptoms.     

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.     

Terrestrial optics in an aquatic eye: The sandlance,Limnichthytes fasciatus (Creediidae,Teleostei)

The sandlance, Limnichthyes fasciatus (Creediidae, Teleostei), behaves like a marine chameleon, with independent movements of its turret-like eyes, highly-effective camouflage and rapid strikes for isolated, mobile prey at close quarters. The optical system has a fixed circular pupil, a deep pit fovea and a flattened lens unlike any other teleost lens so far described. The convex, laminated structure of the cornea is also unparalleled in a teleost which suggests that the cornea may play a refractive role that might compensate for the reduced power of the flattened lens. This suggestion has been supported in the present investigation by four independent sets of observations:- i. Purkinje images formed underwater by the cornea; ii. Measurements of the magnification of intra-corneal iridophores viewed through the corneal lenticle; iii. Measurements of the magnification produced by the dissected corneal lenticle and lens when viewed over a grating; iv. Ray tracing experiments comparing the degree of refraction produced by the lens and by the corneal lenticle. All experimental observations confirm that the cornea of the sandlance has a significant refractive role, with a power of approximately 200 D compared with a power of 550 D for the lens. This is the first report of a significant refractive role played by the cornea in a teleost. The optical system of lens plus cornea, in combination with a deep pit fovea, may be more suitable for the detection and visual localisation of small, moving, underwater prey than the conventional wide-field spherical lens system of other teleosts. The evolutionary convergence of this marine optical system and lifestyle with those of the chameleon is remarkable, given the constraints imposed by underwater optics.     

Light transmission in the human cornea as a function of position across the ocular surface: theoretical and experimental aspects

This article investigates the theoretical basis for differences in visible light transmission through the human cornea as a function of distance from the center. Experimentally, transmission decreases approximately linearly up to 3 mm from the central axis, then quadratically beyond this. It is known that collagen fibril number density and collagen fibril radii change from the central region to the corneal periphery. We modeled, using the direct-summation-of-scattered-fields method, the effects these ultrastructural changes would be expected to have on light transmission, accounting for the increase in corneal thickness from center to edge. Fibril positions for the modeling were obtained from electron micrographs of human cornea. Theoretically, transmission remains fairly constant across the central cornea; then, as the fibril diameter increases, the predicted scattering increases. Interfibrillar spacing changes alter the refractive index ratio between matrix and fibril; this was modeled in our theoretical deductions. Fibril number density had a minimal effect on light propagation. Our theoretical deductions were in broad agreement with our experimental data. It is concluded that the reduced transparency in the peripheral stroma is primarily caused by changes in fibril radius and an increase in refractive index ratio between the fibril and the interfibrillar substance.