Cornea In Order Research Articles

A Mechanical Evaluation of a Robot-Assisted Cutting Cornea Based on Force Response.

The aim of this paper is to propose laws of trephine operation based on a robot-assisted cutting cornea in order to obtain better microsurgical effects for keratoplasty. Using a trephine robot integrated with a microforce sensor and a handheld trephine manipulator, robotic and manual experiments were performed, with porcine corneas as the test subjects. The effect of trephine operational parameters on the results reflected by the biomechanical response is discussed, and the parameters include linear velocity, rotating angle, and angular velocity. Using probability density functions, the distributions of the manual operational parameters show some randomness, and there is a large fluctuation in the trephine force during the experiments. The biomechanical response shows regular trends in the robotic experiments even under different parameters, and compared to manual trephination, the robot may perform the operation of trephine cornea cutting more stably. Under different operational parameters, the cutting force shows different trends, and the optimal initial parameters that result in better trephine effects can be obtained based on the trends. Based on this derived law, the operational parameters can be set in robotic trephination, and surgeons can also be specially trained to achieve a better microsurgical result.

Principles of corneal cross-linking : Presentation based on the development of the various treatment protocols

Corneal cross-linking (CXL) is used to treat corneal ectatic diseases. The aim is to improve the reduced consolidation of the cornea in order to halt further corneal protrusion and therefore subsequent deterioration of the optical imaging proportions. In this article the principles of corneal cross-linking based on riboflavin and UV light are presented including recent research results. Furthermore, the most important treatment protocols including standard CXL (S-CXL), accelerated CXL (A-CXL), transepithelial CXL (TE-CXL) and the approach of the CXL procedure for thin corneas are explained. The CXL method depends on four major components, the riboflavin solution, oxygen, UV light and the availability of cross-linking sites on the collagen tissue. According to the present state of knowledge, the photochemical process of the CXL method induces covalent bonds between the fibrils and proteoglycans and thus stabilizes the collagen fibers, resulting in corneal consolidation. In addition to the S‑CXL, which has proven its effectiveness and safety in alarge number of studies, there are other treatment protocols that have been developed based on the Bunsen-Roscoe law of reciprocity. The A‑CXL protocol has the advantage of having ashorter irradiation time but it seems to be less effective than the S‑CXL protocol concerning the increase in corneal stiffness. The use of TE-CXL has so far not yet gained acceptance in the clinical practice. The CXL procedures primarily aim to stabilize the cornea. In the future, in addition to stabilization of the cornea, simultaneous improvement of visual acuity will be the main focus.

Лечение ятрогенной отслойки десцеметовой мембраны после факоэмульсификации катаракты с имплантацией интраокулярной линзы. Анализ проблемы и клинический случай

Purpose. To evaluate the efficiency of the complex treatment of Descemet’s membrane detachment. Material and methods. In case of failure of therapeutic methods of treatment of induced keratopathy, a 65-year patient underwent an optical coherence tomography of the anterior segment, and a total detachment of the Descemet’s membrane was detected. The injection of sterile air was performed into the anterior chamber of the patient and the transepithelial puncture of the cornea was carried out in order to drain the fluid located between the Descemet’s membrane and the posterior surface of the corneal stroma. Results. The patient underwent pneumopexy of the Descemet’s membrane with transepithelial puncture of the cornea in order to drain the fluid located between the Descemet’s membrane and the posterior surface of the corneal stroma associated with the standard keratoplastic and anti-inflammatory therapy. The postoperative period was without complications. During the examination a week later, a complete absence of subjective symptoms (pain, lacrimation, foreign body sensation, photophobia) was revealed, objectively the edema of all corneal layers was significantly reduced. The visual acuity of the operated eye increased from 0.05 n/c to 1.0. Conclusion. In case of total detachment of the Descemet’s membrane the application of thee sterile air injection into the anterior chamber with the transepithelial puncture of the cornea in order to drain the fluid between the Descemet’s membrane and the posterior surface of the corneal stroma, leads to its complete attachment, an arrest of the corneal syndrome and an improvement of visual acuity.

Endogenous fluorescence can differentiate the keratoconic cornea

The purpose of the study was to investigate the endogenous fluorescence of the keratoconic cornea in order to analyze changes in the spectra due to the keratoconic stroma abnormalities.Twenty-two corneal buttons obtained from patients with keratoconus (KC, N = 22) at the time of penetrating keratoplasty were used. As a reference, twelve normal corneas (N = 12): ten from the Eye Bank and two from enucleated eyes due to choroidal melanoma were used. The fluorescence excitation/emission matrices (EEM) in the ranges of 250–400/260–600 nm were recorded.Healthy cornea, keratoconic cornea and sclera showed three main EEM bands, which correspond to the following fluorophores: tryptophan residues in the proteoglycan fraction of corneal/scleral stromas, naturally occurring collagen cross-links and the NAD(P)H fraction present in the metabolically active cells. Relative intensity factors S1, S2 and S3 describing the contribution of each kind of fluorophore to the total fluorescence of the tissue were calculated. Normal and keratoconic corneas show qualitatively similar fluorescence matrices, but the statistically significant differences in the mean values of the S1, S2 and S3 parameters for the KC and normal corneas were observed indicating changes in contribution of different fluorophores to the whole fluorescence of the tissue. Moreover, differences between multidimensional distribution of the relative intensity factors S1, S2 and S3 between these groups were demonstrated (p < 0.001).In conclusions: Differences in the relative intensity factors calculated on a basis of the fluorescence spectra can correspond to the changes found in the KC stroma regarding natural collagen cross-links and the proteoglycan fraction. These parameters well differentiate the KC and normal corneas that could serve as an additional tool for the keratoconus characterization.

Current concepts and future developments of corneal cross-linking.

The introduction of corneal cross-linking (CXL) has changed the landscape of treatment and management of keratoconus and ectasia after refractive surgery. Previously, treatment options provided only temporary visual rehabilitation without limiting disease progression. Keratoconus and ectasia resulted in significant vision-related reduction in quality of life and a substantial lifetime economic burden, with up to 20% of keratoconus cases resulting in eventual corneal transplantation [1]. CXL was introduced as the first therapeutic option for keratoconus aimed at stiffening the cornea in order to treat the underlying stromal instability. From the time that the first reports of the clinical application of cross-linking in the cornea were published in 2003 [2], CXL has rapidly been adopted as a standard therapy for treatment of progressive keratoconus in much of the world [3–5]. The potential for early intervention with corneal cross-linking before visual function has been compromised has resulted in a shift in the way we think about corneal biomechanics and has reawakened interest in the early diagnosis of ectasia. In this issue, J. Steinberg et al. report two new parameters to detect biomechanical changes in the keratoconic cornea after CXL using in vivo corneal visualization Scheimpflug technology. Research in the area of corneal biomechanics has the potential to enable earlier diagnosis of patients in need of CXL and better analysis of the effects of the procedure. While many questions remain unanswered, the understanding of the photochemical mechanisms that result in the formation of cross-links in the cornea has grown exponentially in the last decade. Improved scientific understanding of the mechanisms of CXL has driven clinical research aimed at optimizing CXL for better efficiency and efficacy [6]. In this issue, A. C. da Paz et al. present a critical review of known and as yet undetermined effects of CXL on corneal structure, biomechanics, and functional aspects. J. Antoun et al. examine patient characteristics that contribute to cross-linking failure to stabilize keratometry and examine the effect of repeat treatments on eyes that have continued to progress after primary CXL. The remaining contributions to the special issue explore modifications to the conventional protocol that incorporate new technology, such as transepithelial riboflavin formulations designed to improve patient comfort (S. Taneri et al.) and higher irradiance and pulsed UVA delivery aimed at improving procedure speed and photon efficiency (C. Mazzotta et al.). CXL combination procedures targeted at maximizing visual outcomes through the addition of simultaneous intracorneal ring implantation (P. Studeny et al.) or subsequent phakic toric implantable collamer lens insertion (R. Antonios et al.) are also discussed. Together, the papers in this special issue describe the next generation of corneal cross-linking. The contributors explore the potential to maximize CXL efficacy, provide equivalent or greater treatment effect in shorter total treatment times, reduce patient discomfort and speed visual recovery, and offer both stabilization and functional visual improvement through CXL combination procedures. Suphi Taneri Elias Jarade John A. Kanellopoulos David Muller

Comparison of Four Methods for Corneal Thickness Measurement

Summary The aim of the study was to evaluate the thickness of the normal cornea in order to establish correlation between four methods of measuring including: ultrasound pachymetry (USP), anterior segment optical coherence tomography (ASOCT), non-contact tono/pachymetry (TONOPACHY) and laser-scanning confocal microscopy (LSCM). The study was based on evaluating repeatability and comparability of four different methods formeasuring the corneal thickness. Non contact specular microscopy was first performed on all 27 patients (aged between 20 and 24 years) to evaluate corneal characteristics and confirm the absence of pathological changes. Each participant was examined by USP, ASOCT and TONOPACHY, and 13 eyes of 10 persons were also examined by LSCM. The values of average central corneal thickness measured by USP, ASOCT, TONOPACHY and LSCM were 532.20±4.5 pm, 553.33±12.1 pm, were 548.20±5.62 pm and 573.33±7.22 pm, respectively. There was a high correlation between the instruments. The mean differences for central corneal thickness measurements were 41.43±1.67 pm between USP and LSCM, 20.43±2.4 pm between USP and ASOCT, and 22.1 ±3.88 pm between USB and TONOPACHY. Anterior segment optical coherence tomography overestimated corneal thickness as compared with that measured by USP, which is believed to be a gold standard. Anterior segment optical coherence tomography had better agreement with USP, as compared with LSCM. However, the results of measured cornea thickness by TONOPACHY were very close to cornea thickness measured by ASOCT.

Simple novel surgical device to facilitate preparation of endothelial grafts for DMEK

AbstractPurpose Descemet’s membrane and endothelial keratoplasty (DMEK) is the only technique to achieve a posterior corneal transplant without any interface. It is however difficult to achieve, mainly during the preparation of the graft. We propose a simple novel surgical device to facilitate this preparation.Methods We used 20 corneas for research in this study. The device is in the form of a circular blade with a diameter of 8.5 mm. The blade is broken in two opposite points on 4 mm. The blade is applied to the cornea in order to cut Descemet's membrane and deep stroma. Preparation of the endothelial graft is performed on an artificial anterior chamber using a simple technique with a 27 gauge cannula to detach Descemet’s membrane. The dissection is performed under the microscope by a corneal bank technician in 8 cases, by a resident in 4 cases by a cataract surgeon in 8 cases. The three operators followed a specific course on the same day of dissection but had never tried to dissect a DMEK graft before. Endothelial cell density (ECD) was measured before dissection and 3 days after storage in organ culture. Histological analysis was performed.Results Descemet graft could be easily dissected in 19 cases and resident failed dissection in one case. ECD was 2534±275 cells/mm² before dissection and 2412+/‐360 cells/mm², after 3 days in organ culture (p&lt;0.01). Histological sections confirm that the cleavage was between DM and posterior stroma.Conclusion We report here a reliable and efficient technique for the preparation of pure descemetic grafts. Commercial interest

Correlation of central and peripheral corneal thickness in healthy corneas

To study the thickness profile of the normal cornea in order to establish any correlation between central and peripheral points. Sixty-seven eyes of 40 patients were subjected to central corneal thickness measurement (CCT) with an ultrasound pachymeter (UP) and corneal thickness mapping with the Oculus Pentacam. The corneal apex thickness (CAT), pupil centre thickness (recorded as CCT and corresponded to CCT of UP) and thickness at the thinnest location (CTL) were obtained and compared with each other. Corneal thickness data at 3 mm and 7 mm temporally, nasally, superiorly and inferiorly from the corneal apex were obtained. The mean corneal thickness values along the 2, 4, 6, 8 and 10 mm diameter concentric circles, with the CTL as the centre, were also obtained. The above data at different points were statistically correlated. There was no significant difference between CCT readings measured by UP and Pentacam (P=0.721). There was high positive correlation between the CAT values and the thickness at 3 mm (R≥0.845, P<0.001) and at 7 mm points (R≥0.654, P<0.001). A gradual increase in thickness was noted from the centre to the periphery with a high positive correlation between the CTL values and the mean thickness at the circles of 2, 4, 6, 8 and 10 mm (R≥0.635, P<0.001). The results suggest that central corneal thickness can serve as a good guide for predicting peripheral thickness. For surgical procedures specifically undertaken at mid-peripheral and peripheral zones, the actual measurements at the site of surgery may confer some advantage.

Keratocyte‐mediated establishment of lamellar structure in corneal development

Abstract Purpose Mechanisms by which presumptive keratocytes in the developing cornea engineer the 3‐dimensional lamellar matrix of the transparent stroma remain unknown. We used Volume Scanning Electron Microscopy to observe lamella formation in embryonic avian cornea in order to understand better corneal stromal biosynthesis, transparency and repair. Methods Corneas were obtained from chick embryos at E10 and E14, when a loose structure of collagen fibril bundles condenses into the lamellar organisation of the mature stroma. Aldehyde‐fixed corneas were contrast‐enhanced in osmium ferricyanide and tannic acid and embedded in Durcupan resin. Toluidine blue‐stained sections were used to locate suitable sites, subsequently examined in unstained ultrathin sections in a Jeol 1010 transmission electron microscope. The polished faces of the resin blocks were then imaged using a BSE detector in a Quanta 3D FEG FIB/SEM via an alternate slice‐and‐view protocol. 50nm slicing was performed with a focused gallium ion beam and image series were collected over 18h. Image stacks were processed using ImageJ software. Results Transmission and volume scanning electron microscopy reveal complex compartmentalisation of developing chick corneal stroma. Keratocyte filopodia extend many microns from cells into the extracellular space. These invest collagen fibrils, with varying orientations, and persist as the stroma condenses, appearing to orchestrate the spatial and directional organisation of the component lamellae. Conclusion Volume SEM reveals in 3D the complex cellular morphology of prospective keratocytes in developing chick cornea with extensive filopodia, which presumably channel and direct collagen fibril bundles into an emergent lamellar architecture.

Decellularization of bovine corneas for tissue engineering applications

Scaffolds derived from processed tissues offer viable alternatives to synthetic polymers as biological scaffolds for regenerative medicine. Tissue-derived scaffolds provide an extracellular matrix (ECM) as the starting material for wound healing and the functional reconstruction of tissues, offering a potentially valuable approach for the replacement of damaged or missing tissues. Additionally, acellular tissue may provide a natural microenvironment for host-cell migration and the induction of stem cell differentiation to contribute to tissue regeneration. There are a number of processing methods that aim to stabilize and provide an immunologically inert tissue scaffold. Furthermore, these tissue-processing methods can often be applied to xenogenic transplants because the essential components of the ECM are often maintained between species. In this study, we applied several tissue-processing protocols to the cornea in order to obtain a decellularized cornea matrix that maintained the clarity and mechanical properties of the native tissue. Histology, mechanical testing and electron microscopy techniques were used to assess the cell extraction process and the organization of the remaining ECM. In vitro cell seeding experiments confirmed the processed corneas’ biocompatibility.

Mediators of Neovascularization and the Hypoxic Cornea

The maintenance of corneal avascularity is essential to vision. The mechanisms by which the cornea becomes vascularized in response to inflammation or hypoxic stress are beginning to be elucidated. A detailed understanding of the molecular responses of the cornea to hypoxia is critical for prevention and development of novel treatments for neovascularization in a range of disease states. Here, we have examined the current literature on the major mediators of angiogenesis, which have previously been reported during hypoxia in the cornea in order to better understand the mechanisms by which corneal angiogenesis occurs in circumstances where the available oxygen is reduced. The normal cornea produces angiogenic factors that are regulated by the production of anti-angiogenic molecules. The various cell types of the cornea respond differentially to inflammatory and hypoxic stimuli. An understanding of the factors that may predispose patients to development of corneal blood vessels may provide an opportunity to develop novel prophylactic strategies. The difficulties with extrapolating data from other cell types and animal models to the cornea are also examined.

Amniotic Membrane Transplantation Associated with Conjunctival Peritomy in the Management of Mooren's Ulcer: A Case Report

To report the association of conjunctival peritomy with amniotic membrane transplantation (AMT) at the limbus with the exclusion of the central cornea in order to preserve visual function in one case of bilateral Mooren's ulcer. A 36-year-old man with bilateral Mooren's ulcer was unresponsive to conventional therapy. Surgical procedure was performed on his right eye, at impending risk of corneal perforation. A 20 x 20 mm piece of amniotic membrane (AM) was prepared by performing a central hole of 7.5 mm diameter with a manual trephine. A 360 degrees conjunctival peritomy was performed and the AM was placed with the epithelium side facing up and the central hole was sutured on the paracentral cornea. Two weeks after surgery, while the right eye showed improvement of signs and symptoms and unchanged best-corrected visual acuity (BCVA), the left eye showed a peripheral corneal perforation with prolapsed iris that required conjunctival flap. At 7 months of follow-up, the right eye showed no ocular inflammation, a reduction of the lipid-like peripheral corneal infiltrates, an increased stromal thickness, and an unchanged BCVA. The progression of corneal thinning in the left eye led the authors to perform AMT (as described) in the left eye as well. Five months after the AMT in the left eye, neither eye shows signs of disease progression, and neither requires further therapy. Conjunctival peritomy associated with AMT may be an alternative surgical approach in the management of Mooren's ulcers to control the inflammation and the progression of disease.

Lamellar orientation in human cornea in relation to mechanical properties

We have applied wide-angle X-ray scattering to the human cornea in order to quantify the relative number of stromal collagen fibrils directed along the two preferred corneal lamellar directions: superior–inferior and nasal–temporal. The data suggest that, on average, the two directions are populated in equal proportion at the corneal centre. Here, approximately one-third of the fibrils throughout the stromal depth tend to lie within a 45° sector of the superior–inferior meridian, and similarly for the nasal–temporal direction. However, in some eyes we have measured significant differences between the two preferential fibril populations, with some corneas exhibiting as much as 25% more collagen in one direction than the other. Based on these findings, a mechanical model of the normal cornea may be envisaged, whereby the fibril tension in the underlying “background” of isotropically arranged collagen helps to balance the intraocular pressure; while the extra preferentially aligned fibrils take up the additional tensile stress along the superior–inferior and nasal–temporal meridians exerted by the rectus muscles and the orbicularis. It is possible that, through a direct impact on the elastic modulus of the tissue, an imbalance of superior–inferior and nasal–temporal fibrils in some eyes might affect corneal shape.

Assessment of stress fiber orientation during healing of radial keratotomy wounds using confocal microscopy.

Radial keratotomy (RK) is a refractive surgical procedure in which partial thickness incisions are made in the cornea in order to alter its shape. Previous studies suggest that RK wounds undergo changes in wound gape in response to the ingrowth of myofibroblasts which mediate subsequent wound contraction and may modulate changes in corneal curvature seen after RK. A recent quantitative analysis of f-actin organization in full-thickness incisional wounds in the rabbit demonstrated that microfilament bundles (stress fibers) present in myofibroblasts align parallel to the long axis of the wound during wound contraction. To investigate whether the same pattern of alignment occurs after RK, a similar analysis of f-actin organization was undertaken using the cat RK model. Radial keratotomy wounds were studied from 10 to 28 days after surgery using en block staining with fluorescein isothiocyanate (FITC) phalloidin, and three-dimensional (3-D) datasets (z-series of en face optical sections) were collected using laser confocal microscopy at various regions within the wound. In addition, conventional en face sections were double-labeled using combinations of phalloidin and antibodies to fibronectin and alpha 5 beta 1 integrin. Myofibroblast ingrowth started in the bottom of the wound and progressed anteriorly. At 10 to 14 days, f-actin was predominantly distributed in long, thick bundles (stress fibers) within the wound. These fibers appeared to be randomly oriented anteriorly, but became progressively more aligned with the long axis of the wound posteriorly. At 21 days, the stress fibers were predominantly oriented parallel to the long axis of the wound at all levels. F-actin, fibronectin and integrin were coaligned at both the 14 and 21 day time points. Since the majority of wound closure occurs between 14 and 28 days after surgery, we conclude that parallel alignment of the actin filament-fibronectin-integrin assembly in the cat RK model is associated with wound contraction.

Inhibitory effects of plasminogen fragment on experimentally induced neovascularization of rat corneas.

Corneal neovascularization plays an important role in the pathogenesis of a number of corneal disorders. Recently a polypeptide was demonstrated, generated by the primary tumor, that inhibited angiogenesis and growth in metastases. This polypeptide is similar to a 38-kDa plasminogen fragment. We surgically implanted into rat corneal stroma a slow-release ethylene-vinyl-acetate (EVA) copolymer pellet containing basic fibroblast growth factor (bFGF) to induce corneal neovascularization. Then we applied aqueous solution containing plasminogen fragment to the rat cornea in order to observe the degree of inhibition of angiogenesis. In the eyes of control rats, neovascularization from the limbus to the pellet occurred, graded 4+ in all five animals. In plasminogen fragment-treated rats, there was virtually complete inhibition of the neovascular response to the pellet. Of five treated rats, three showed no neovascularization and two demonstrated grade 1+ neovascularization. The difference in the degree of neovascularization between control and plasminogen fragment treatment was statistically significant (P < 0.05). Our studies provide the first direct evidence that rat corneal neovascularization is inhibited by instillation of plasminogen fragment. This agent may prove useful in the treatment of corneal angiogenic disorder.

Analytical Model of Corneal Surgery

We present a model of the human cornea in order to study the changes in its shape resulting from surgical operations (e.g., radial keratotomy). A simple closed-form solution is given for a thin linearly elastic spherical shell model of the cornea. We assume axisymmetry and isotropy in the shell surface. The surgery is modeled by permitting Young's modulus and shell thickness to depend on position. The analytical nature of the solution permits principal shell curvatures to be explicitly calculated. The model is used to investigate the effect of surgery on corneal flattening and the associated sensitivity to intraocular pressure changes.

Localization of Intraocular Foreign Bodies by Roentgen Examination

Technique Take plain films: front and side views of the suspected eye. Reference lines: With some drops of 0.5% tetracaine (Pontocaine) solution anesthetize the eye, in order to attach at the sclerocorneal limbus the regular nonabsorbable surgical (silk) Atraumatic suture needles (⅜ circle ⅝ in. long, preferably).* The needles are passed through the conjunctiva and Tenon's capsule as close as possible to the cornea, starting about 1.5 mm. above and below the 3 o'clock or 9 o'clock position on the cornea, trying to mark the limbus surrounding the cornea in order to get its center. Immediately take the following films: Front view: looking straight ahead, both orbits; central ray focused on the center of the cornea Front view: looking right, both orbits Front view: looking left, both orbits Front view: looking up, both orbits Front view: looking down, both orbits The films B, C, D and E should be taken without

KERATECTOMIES FOR TREATMENT OF CORNEAL OPACITIES

The surgical treatment of corneal opacities has been in use for over two centuries. Boury,1in 1743; Plenck,2in 1783; Bertrandi,3in 1798; Wenzel,4in 1808 ; Demours,5in 1821 ; Rosas,6in 1830; Carron du Villards,7in 1838; Chelius,8in 1839; Cappelletti,9in 1844, and Desmarres,10in 1847, spoke of scarifications and abrasions of the cornea. Small, nonperforating punctures made with a knife or needles in the cornea in order to provoke inflammatory processes tending to clear up the opacities were advocated by Ware,11in 1795 ; by Holchers,12in 1842, and by Himley,13in 1843. Riveri,14in 1836, advocated paracentesis of the anterior chamber to improve the vision of eyes with corneal opacities, especially those with abundant vascularization. Another surgical procedure used to improve vision in eyes affected with corneal opacities consists in the excision of the