High resolution immunoelectron microscopic localization of functional domains of laminin, nidogen, and heparan sulfate proteoglycan in epithelial basement membrane of mouse cornea reveals different topological orientations

Thin and ultrathin cryosections of mouse cornea were labeled with affinity-purified antibodies directed against either laminin, its central segments (domain 1), the end of its long arm (domain 3), the end of one of its short arms (domain 4), nidogen, or low density heparan sulfate proteoglycan. All basement membrane proteins are detected by indirect immunofluorescence exclusively in the epithelial basement membrane, in Descemet's membrane, and in small amorphous plaques located in the stroma. Immunoelectron microscopy using the protein A-gold technique demonstrated laminin domain 1 and nidogen in a narrow segment of the lamina densa at the junction to the lamina lucida within the epithelial basement membrane. Domain 3 shows three preferred locations at both the cellular and stromal boundaries of the epithelial basement membrane and in its center. Domain 4 is located predominantly in the lamina lucida and the adjacent half of the lamina densa. The low density heparan sulfate proteoglycan is found all across the basement membrane showing a similar uniform distribution as with antibodies against the whole laminin molecule. In Descemet's membrane an even distribution was found with all these antibodies. It is concluded that within the epithelial basement membrane the center of the laminin molecule is located near the lamina densa/lamina lucida junction and that its long arm favors three major orientations. One is close to the cell surface indicating binding to a cell receptor, while the other two are directed to internal matrix structures. The apparent codistribution of laminin domain 1 and nidogen agrees with biochemical evidence that nidogen binds to this domain.

Die Behandlung der Hornhaut-Trübungen mit besonderer Berücksichtigung der Einsetzung einer künstlichen Hornhaut (Cornea artificalis)

von J. Nußbaum

A case-control study of the association between corneal arcus and death by cardiovascular disease among cornea donors

The cornea of the human eye can develop deposits of lipids in the periphery known as corneal arcus. [2, 10] For over a century, these deposits have been of interest as possible indicators of the accumulation of lipids in arterial walls of the heart and body with implications for heart disease. [2, 10, 11, 29] Heart disease is currently the leading cause of death in this country. [5, 29] There have been several publications suggesting an association between the development of atherosclerotic lesions and corneal arcus. [2, 12, 29] Investigators have differed in their interpretation of the relevance of corneal arcus to coronary heart disease or cardiovascular disease. However, there is widespread consensus that the presence of corneal arcus in patients under the age of 50 should prompt physicians to further investigate for dyslipidemia or heart disease. [2, 3, 6, 8, 19] Earlier studies have often suffered from difficulty in determining the presence or severity of atherosclerosis and from inconsistencies in evaluating corneal arcus. This study involves the review of mortality data, medical and social history and standardized slit lamp examination of corneal tissue donors to evaluate the prevalence of corneal arcus in relation to death by CHD or CVD. The prevalence of arcus, odds ratio, and logistic regression was utilized for statistical analysis.^

Aldehyde dehydrogenase class 3 expression: Identification of a cornea-preferred gene promoter in transgenic mice

Aldehyde dehydrogenase class 3 (ALDH3) constitutes 20–40% of the total water-soluble proteins in the mammalian cornea. Here, we show by Northern blot analysis that ALDH3 expression in the mouse is at least 500-fold higher in the cornea than in any other tissue examined, with very low levels of expression detected in the stomach, urinary bladder, ocular lens, and lung. Histochemical localization reveals that this exceptional level of expression in the mouse cornea occurs in the anterior epithelial cells and that little ALDH3 is present in the keratocytes or corneal endothelial cells. A 13-kbp mouse ALDH3 promoter fragment containing >12 kbp of the 5′ flanking sequence, the 40-bp untranslated first exon, and 29 bp of intron 1 directed cat reporter gene expression to tissues that express the endogenous ALDH3 gene, except that transgene promoter activity was higher in the stomach and bladder than in the cornea. By contrast, when driven by a 4.4-kbp mouse ALDH3 promoter fragment [1,050-bp 5′ flanking region, exon 1, intron 1 (3.4 kbp), and 7 bp of exon 2] expression of the cat reporter gene was confined to the corneal epithelial cells, except for very low levels in the liver, effectively reproducing the corneal expression pattern of the endogenous ALDH3 gene. These results indicate that tissue-specific expression of ALDH3 is determined by positive and negative elements in the 5′ flanking region of the gene and suggests putative silencers located in intron 1. We demonstrate regulatory sequences capable of directing cornea-specific gene expression, affording the opportunity for genetic engineering in this transparent tissue.

Coupled Biomechanical Response of the Cornea Assessed by Non-Contact Tonometry. A Simulation Study

The mechanical response of the cornea subjected to a non-contact air-jet tonometry diagnostic test represents an interplay between its geometry, the corneal material behavior and the loading. The objective is to study this interplay to better understand and interpret the results obtained with a non-contact tonometry test. A patient-specific finite element model of a healthy eye, accounting for the load free configuration, was used. The corneal tissue was modeled as an anisotropic hyperelastic material with two preferential directions. Three different sets of parameters within the human experimental range obtained from inflation tests were considered. The influence of the IOP was studied by considering four pressure levels (10–28 mmHg) whereas the influence of corneal thickness was studied by inducing a uniform variation (300–600 microns). A Computer Fluid Dynamics (CFD) air-jet simulation determined pressure loading exerted on the anterior corneal surface. The maximum apex displacement showed a linear variation with IOP for all materials examined. On the contrary, the maximum apex displacement followed a cubic relation with corneal thickness. In addition, a significant sensitivity of the apical displacement to the corneal stiffness was also obtained. Explanation to this behavior was found in the fact that the cornea experiences bending when subjected to an air-puff loading, causing the anterior surface to work in compression whereas the posterior surface works in tension. Hence, collagen fibers located at the anterior surface do not contribute to load bearing. Non-contact tonometry devices give useful information that could be misleading since the corneal deformation is the result of the interaction between the mechanical properties, IOP, and geometry. Therefore, a non-contact tonometry test is not sufficient to evaluate their individual contribution and a complete in-vivo characterization would require more than one test to independently determine the membrane and bending corneal behavior.

New-Generation Hybrid Contact Lens for the Management of Extreme Irregularity in a Thin Cornea After Unsuccessful Excimer Laser Refractive Surgery

Purpose: To report a very successful outcome obtained with the fitting of a new-generation hybrid contact lens of reverse geometry in a thin cornea with extreme irregularity due to the presence of a central island after unsuccessful myopic excimer laser refractive surgery. Methods: A 32-year-old man attended to our clinic complaining of very poor vision in his right eye after bilateral laser in situ keratomileusis (treatment or surgery) for myopia correction and some additional retreatments afterward. After a comprehensive ocular evaluation, contact lens fitting with a reverse geometry hybrid contact lens (SynergEyes PS, SynergEyes, Carlsbad, CA) was proposed as a solution for this case. Visual, refractive, and ocular aberrometric outcomes with the contact lens were evaluated. Results: Distance visual acuity improved from a prefitting uncorrected value of 20/200 to a postfitting corrected value of 20/16. Prefitting manifest refraction was +6.00 sphere and −3.00 cylinder at 70°, with a corrected distance visual acuity of 20/40. Higher order root mean square for a 5-mm pupil changed from a prefitting value of 1.45 to 0.34 µm with the contact lens. The contact lens wearing was reported as comfortable, and the patient was very satisfied with this solution. Conclusions: The SynergEyes PS contact lens seems to be an excellent option for the visual rehabilitation of corneas with extreme irregularity after myopic excimer laser surgery, minimizing the level of higher order aberrations and providing an excellent visual outcome.

Disertacion sobre las ulceras de los ojos que interesan la cornea transparente... /

Marca tipográfica en la portada.

Saggio d'ecraxis o Particolari di talune operazioni di cateratte, seguite dal modo di curar le ulceri della cornea e la procidenza dell'iride, indi la demolizione di un tumore fungoso della cornea /

Mode of access: Internet.

An essay on the ophthalmia or inflammation of the eyes and the diseases of the transparent cornea : : with improvements in the methods of cure /

Mode of access: Internet.

Quaestio medico-chirurgica quodlibetariis disputationibus manè discutienda, in Scholis Medicorum ... Anno Domini MDCCLXVI ... Utriùm in curando hypopyo incisioni cornea praestet embroche? /

Mode of access: Internet.

First development of a polyurethane keratoprosthesis and its Australian connection: An unbeknown episode in the history of artificial cornea

This paper is aimed at establishing a particular chronological priority issue in the convoluted history of artificial cornea. According to existing records, the first keratoprosthesis made from polyurethane was developed by Caldwell and Jacob-Labarre in the late 1980s. This paper demonstrates that in fact the first polyurethane keratoprosthesis was proposed and designed in 1985 by Lawrence Hirst, an Australian ophthalmologist then working in St Louis, USA. The first prototype was manufactured in January 1986 by Thermedics Inc according to Dr Hirst's instructions from Tecoflex, a transparent polyurethane developed by the same company. This keratoprosthesis, which also had a porous skirt, was inserted intralamellarly in a monkey cornea and followed up clinically for about 3 months. There were no significant postoperative complications, and the histology of the explant indicated proper biointegration of the prosthetic skirt within the host stromal tissue. Because of a delay in the manufacture of further prototypes and to Dr Hirst's decision to return to Australia, the project was eventually abandoned. As no report was published on this development, the present paper is entirely based on original documents held in Dr Hirst's archives.

Accuracy of cornea and lens biometry using anterior segment optical coherence tomography

We assess the accuracy of the Visante anterior segment optical coherence tomographer (AS-OCT) and present improved formulas for measurement of surface curvature and axial separation. Measurements are made in physical model eyes. Accuracy is compared for measurements of corneal thickness (d1) and anterior chamber depth (d2) using-built-in AS-OCT software versus the improved scheme. The improved scheme enables measurements of lens thickness (d 3) and surface curvature, in the form of conic sections specified by vertex radii and conic constants. These parameters are converted to surface coordinates for error analysis. The built-in AS-OCT software typically overestimates (mean±standard deviation(SD)]d1 by +62±4 μm and d2 by +4±88μm. The improved scheme reduces d1 (-0.4±4 μm) and d2 (0±49 μm) errors while also reducing d3 errors from +218±90 (uncorrected) to +14±123 μm (corrected). Surface x coordinate errors gradually increase toward the periphery. Considering the central 6-mm zone of each surface, the x coordinate errors for anterior and posterior corneal surfaces reached +3±10 and 0±23 μm, respectively, with the improved scheme. Those of the anterior and posterior lens surfaces reached +2±22 and +11±71 μm, respectively. Our improved scheme reduced AS-OCT errors and could, therefore, enhance pre- and postoperative assessments of keratorefractive or cataract surgery, including measurement of accommodating intraocular lenses. © 2007 Society of Photo-Optical Instrumentation Engineers.

A biological-inspired support frame for an artificial cornea

Bilateral corneal blindness represents a quarter of the total blind, world-wide. The artificial cornea in assorted forms, was developed to replace opaque non-functional corneas and to return sight in otherwise hopeless cases that were not amenable to corneal grafts; believed to be 2% of corneal blind. Despite technological advances in materials design and tissue engineering no artificial cornea has provided absolute, long-term success. Formidable problems exist, due to a combination of unpredictable wound healing and unmanageable pathology. To have a solid guarantee of reliable success an artificial cornea must possess three attributes: an optical window to replace the opaque cornea; a strong, long term union to surrounding ocular tissue; and the ability to induce desired host responses. A unique artificial cornea possesses all three functional attributes- the Osteo-odonto-keratoprosthesis (OOKP). The OOKP has a high success rate and can survive for up to twenty years, but it is complicated both in structure and in surgical procedure; it is expensive and not universally available. The aim of this project was to develop a synthetic substitute for the OOKP, based upon key features of the tooth and bone structure. In doing so, surgical complexity and biological complications would be reduced. Analysis of the biological effectiveness of the OOKP showed that the structure of bone was the most crucial component for implant retention. An experimental semi-rigid hydroxyapatite framework was fabricated with a complex bone-like architecture, which could be fused to the optical window. The first method for making such a framework, was pressing and sintering of hydroxyapatite powders; however, it was not possible to fabricate a void architecture with the correct sizes and uniformity of pores. Ceramers were synthesised using alternative pore forming methods, providing for improved mechanical properties and stronger attachment to the plastic optical window. Naturally occurring skeletal structures closely match the structural features of all forms of natural bone. Synthetic casts were fabricated using the replamineform process, of desirable natural artifacts, such as coral and sponges. The final method of construction by-passed ceramic fabrication in favour of pre-formed coral derivatives and focused on methods for polymer infiltration, adhesion and fabrication. Prototypes were constructed and evaluated; a fully penetrative synthetic OOKP analogue was fabricated according to the dimensions of the OOKP. Fabrication of the cornea shaped OOKP synthetic analogue was also attempted.

Dimensional changes in the ageing cornea

The study investigated the central and peripheral corneal characteristics of groups of subjects from 20 to 90 years of age to assist the understanding of ageing changes in the cornea, and to see whether relationships between ocular parameters were revealed. After age 45 the corneal horizontal radius of curvature gradually decreased with age. This trend was shown by the Aston University subjects (group B). The effect was very significant for the hospital patients undergoing biometry before cataract extraction operation (group D). Vertical radius of curvature showed a slight decrease with age after age 45, but similar to corneal eccentricity, this showed no significant age effect. Corneal astigmatism progressed from with the rule towards against the rule, particularly after age 60. The shift seemed mainly due to the decreasing horizontal corneal curvature. In biometry no significant age relation was found for axial length, but a significant relation was found between curvature and axial length in the larger group D. Lens thickness showed a very significant relation to age and to axial length, but no significant relation to corneal curvature. Anterior chamber depth showed a very significant relation to age, lens thickness and axial length, but no significant relation to corneal curvature. A significant age effect was found for corneal thickness decreasing with age for the central, nasal and temporal regions of the right eye. Analysis of the biometry results indicated the influence of two major factors. Firstly, the natural growth of the eye in youth, leading to greater values of axial length, radius of corneal curvature, lens thickness and anterior chamber depth. Secondly, the typical ageing changes where the increasing lens thickness caused a reduction in anterior chamber depth. The decrease in corneal thickness with age shown in some corneal regions may be a sign of ageing changes in the tissue proteins and hydration balance.