Gartry, D.; Kerr Muir, M.; Marshall, J.
The argon fluoride excimer laser emits radiation in the far ultraviolet part of the electromagnetic spectrum (193 nm). Each photon has high individual energy. Exposure of materials or tissues with peak absorption around 193 nm results in removal of surface layers (photoablation) with extremely high precision and minimal damage to non-irradiated areas. This precision is confirmed in a series of experiments on cadaver eyes and the treatment of 25 eyes with anterior corneal disease (follow-up 6 to 30 months). Multiple zone excimer laser superficial keratectomy is considered the treatment of choice for rough, painful corneal surfaces. All patients in this group were pain-free postoperatively. Where good visual potential exists, ablation of a single axial zone is recommended and results in improved visual acuity and reduction of glare. A hyperopic shift was noted in this group. Images PMID:1817467
Schwab, I R
PURPOSE: To evaluate the potential efficacy for autologous and allogeneic expanded corneal epithelial cell transplants derived from harvested limbal corneal epithelial stem cells cultured in vitro for the management of ocular surface disease. METHODS: Human Subjects. Of the 19 human subjects included, 18 (20 procedures) underwent in vitro cultured corneal epithelial cell transplants using various carriers for the epithelial cells to determine the most efficacious approach. Sixteen patients (18 procedures on 17 eyes) received autologous transplants, and 2 patients (1 procedure each) received allogeneic sibling grafts. The presumed corneal epithelial stem cells from 1 patient did not grow in vitro. The carriers for the expanded corneal epithelial cells included corneal stroma, type 1 collagen (Vitrogen), soft contact lenses, collagen shields, and amniotic membrane for the autologous grafts and only amniotic membrane for the allogeneic sibling grafts. Histologic confirmation was reviewed on selected donor grafts. Amniotic membrane as carrier. Further studies were made to determine whether amniotic membrane might be the best carrier for the expanding corneal epithelial cells. Seventeen different combinations of tryspinization, sonication, scraping, and washing were studied to find the simplest, most effective method for removing the amniotic epithelium while still preserving the histologic appearance of the basement membrane of the amnion. Presumed corneal epithelial stem cells were harvested and expanded in vitro and applied to the amniotic membrane to create a composite graft. Thus, the composite graft consisted of the amniotic membrane from which the original epithelium had been removed without significant histologic damage to the basement membrane, and the expanded corneal epithelial stem cells, which had been applied to and had successfully adhered to the denuded amniotic membrane. Animal model. Twelve rabbits had the ocular surface of 1 eye damaged in a standard
Karaçorlu, M A; Cakiner, T; Saylan, T
Leprosy is one of the leading causes of corneal hyposensitivity. In this article the corneal sensitivity of 143 leprosy patients was examined, and correlations between corneal hyposensitivity and anterior segment pathology were detected. Twenty four healthy volunteers were examined as controls. Various degrees of corneal loss of sensitivity were found in 46.2% of leprosy patients. Lagophthalmos, chronic lepromatous granulomatous uveitis, iris atrophy, and social blindness were found 4.5-16.6 times more frequently in eyes which developed severe corneal hyposensitivity.
Karaçorlu, M A; Cakiner, T; Saylan, T
Leprosy is one of the leading causes of corneal hyposensitivity. In this article the corneal sensitivity of 143 leprosy patients was examined, and correlations between corneal hyposensitivity and anterior segment pathology were detected. Twenty four healthy volunteers were examined as controls. Various degrees of corneal loss of sensitivity were found in 46.2% of leprosy patients. Lagophthalmos, chronic lepromatous granulomatous uveitis, iris atrophy, and social blindness were found 4.5-16.6 times more frequently in eyes which developed severe corneal hyposensitivity. PMID:1995039
Compañ, Vicente; Aguilella-Arzo, Marcel; Weissman, Barry A
Oxygen is essential for aerobic mammalian cell physiology. Oxygen tension (PO2) should reach a minimum at some position within the corneal stroma, and oxygen flux should be zero, by definition, at this point as well. We found the locations and magnitudes of this "corneal equilibrium flux" (xmin) and explored its physiological implications. We used an application of the Monod kinetic model to calculate xmin for normal human cornea as anterior surface PO2 changes from 155 to 20 mmHg. We find that xmin deepens, broadens, and advances from 1.25 μm above the endothelial-aqueous humor surface toward the epithelium (reaching a position 320 μm above the endothelial-aqueous humor surface) as anterior corneal surface PO2 decreases from 155 to 20 mmHg. Our model supports an anterior corneal oxygen flux of 9 μL O2 · cm · h and an epithelial oxygen consumption of approximately 4 μL O2 · cm · h. Only at the highest anterior corneal PO2 does our model predict that oxygen diffuses all the way through the cornea to perhaps reach the anterior chamber. Of most interest, corneal oxygen consumption should be supported down to a corneal surface PO2 of 60 to 80 mmHg but declines below this range. We conclude that the critical oxygen tension for hypoxia induced corneal swelling is more likely this range rather than a fixed value.
Zhou, Hong-Yan; Hao, Ji-Long; Bi, Miao-Miao; Wang, Shuang; Zhang, Hong; Zhang, Wen-Song
AIM Excessive dissolve of corneal tissue induced by MMPs which were activated by cytokins and chemokines will lead to corneal ulcer. The molecular mechanism of Lipoxin A4 (LXA4) on corneal collagen degradation in three dimensions was investigated. METHODS Rabbit corneal fibroblasts were harvested and suspended in serum-free MEM. Type I collagen, DMEM, collagen reconstitution buffer and corneal fibroblast suspension were mixed on ice. The resultant mixture solidified in an incubator, after which test reagents and plasminogen was overlaid and the cultures were returned to the incubator. The supernatants from collagen gel incubations were collected and the amount of hydroxyproline in the hydrolysate was measured. Immunoblot analysis of MMP-1, -3 and TMMP-1,-2 was performed. MMP-2,-9 was detected by the method of Gelatin zymography. Cytotoxicity assay was measured. RESULTS LXA4 inhibited corneal collagen degradation in a dose and time manner. LXA4 inhibited the IL-1β induced increases in the pro-MMP-1, -2, -3, -9 and active MMP-1, -2, -3, -9 in a concentration dependent manner. LXA4 could also inhibit the IL-1β induced increases in TIMP-1, -2. CONCLUSION As a potent anti-inflammation reagent, LXA4 can inhibit corneal collagen degradation induced by IL-1β in corneal fibroblasts thus inhibiting corneal dissolving pathology process. PMID:23550231
Balestrazzi, Angelo; Martone, Gianluca; Pichierri, Patrizia; Tosi, Gian Marco; Caporossi, Aldo
We describe an unusual case of ocular surface squamous neoplasia (OSSN) that occurred in a male patient after superonasal clear corneal phacoemulsification with extensive papillomatous corneal invasion near a side port. The features of the macroscopic invasion of the corneal superficial layers were analyzed by in vivo confocal analysis using the Heidelberg Retina Tomograph II. After OSSN was diagnosed, topical mitomycin-C 0.02% eyedrops were prescribed 4 times a day in a cyclic manner (3 cycles of 1 week on drops followed by 1 week off). After 1 month (second cycle), the natural visual acuity was 20/20, the corneal epithelium had healed completely, and the limbal lesion had regressed markedly. The patient remained asymptomatic without recurrence during a 6-month follow-up.
Chen*, Wei-Sheng; Cao, Zhiyi; Leffler, Hakon; Nilsson, Ulf J.; Panjwani, Noorjahan
Purpose Corneal neovascularization and scarring commonly lead to significant vision loss. This study was designed to determine whether a small-molecule inhibitor of galectin-3 can inhibit both corneal angiogenesis and fibrosis in experimental mouse models. Methods Animal models of silver nitrate cautery and alkaline burn were used to induce mouse corneal angiogenesis and fibrosis, respectively. Corneas were treated with the galectin-3 inhibitor, 33DFTG, or vehicle alone and were processed for whole-mount immunofluorescence staining and Western blot analysis to quantify the density of blood vessels and markers of fibrosis. In addition, human umbilical vein endothelial cells (HUVECs) and primary human corneal fibroblasts were used to analyze the role of galectin-3 in the process of angiogenesis and fibrosis in vitro. Results Robust angiogenesis was observed in silver nitrate–cauterized corneas on day 5 post injury, and markedly increased corneal opacification was demonstrated in alkaline burn–injured corneas on days 7 and 14 post injury. Treatment with the inhibitor substantially reduced corneal angiogenesis and opacification with a concomitant decrease in α-smooth muscle actin (α-SMA) expression and distribution. In vitro studies revealed that 33DFTG inhibited VEGF-A–induced HUVEC migration and sprouting without cytotoxic effects. The addition of exogenous galectin-3 to corneal fibroblasts in culture induced the expression of fibrosis-related proteins, including α-SMA and connective tissue growth factor. Conclusions Our data provide proof of concept that targeting galectin-3 by the novel, small-molecule inhibitor, 33DFTG, ameliorates pathological corneal angiogenesis as well as fibrosis. These findings suggest a potential new therapeutic strategy for treating ocular disorders related to pathological angiogenesis and fibrosis. PMID:28055102
Iqbal, S.; Gualini, M. M. S.
In view of the fast advancement in ophthalmic technology and corneal surgery, there is a strong need for the comprehensive mapping and characterization techniques for corneal surface. Optical methods with precision non-contact approaches have been found to be very useful for such bio measurements. Along with the normal mapping approaches, elasticity of corneal surface has an important role in its characterization and needs to be appropriately measured or estimated for broader diagnostics and better prospective surgical results, as it has important role in the post-op corneal surface reconstruction process. Use of normal corneal topographic devices is insufficient for any intricate analysis since these devices operate at relatively moderate resolution. In the given experiment, Pulsed Electronic Speckle Pattern Interferometry has been utilized along with an excitation mechanism to measure the dynamic response of the sample cornea. A Pulsed ESPI device has been chosen for the study because of its micron-level resolution and other advantages in real-time deformation analysis. A bovine cornea has been used as a sample in the subject experiment. The dynamic response has been taken on a chart recorder and it is observed that it does show a marked deformation at a specific excitation frequency, which may be taken as a characteristic elasticity parameter for the surface of that corneal sample. It was seen that outside resonance conditions the bovine cornea was not that much deformed. Through this study, the resonance frequency and the corresponding corneal deformations are mapped and plotted in real time. In these experiments, data was acquired and processed by FRAMES plus computer analysis system. With some analysis of the results, this technique can help us to refine a more detailed corneal surface mathematical model and some preliminary work was done on this. Such modelling enhancements may be useful for finer ablative surgery planning. After further experimentation
Kass-Iliyya, Lewis; Javed, Saad; Gosal, David; Kobylecki, Christopher; Marshall, Andrew; Petropoulos, Ioannis N.; Ponirakis, Georgios; Tavakoli, Mitra; Ferdousi, Maryam; Chaudhuri, Kallol Ray; Jeziorska, Maria; Malik, Rayaz A.; Silverdale, Monty A.
Autonomic and somatic denervation is well established in Parkinson's disease (PD). Objectives (1) To determine whether corneal confocal microscopy (CCM) can non-invasively demonstrate small nerve fiber damage in PD. (2) To identify relationships between corneal nerve parameters, intraepidermal nerve fiber density (IENFD) and clinical features of PD. Methods Twenty-six PD patients and 26 controls underwent CCM of both eyes. 24/26 PD patients and 10/26 controls underwent skin biopsies from the dorsa of both feet. PD patients underwent assessment of parasympathetic function [deep breathing heart rate variability (DB-HRV)], autonomic symptoms [scale for outcomes in Parkinson's disease – autonomic symptoms (SCOPA-AUT)], motor symptoms [UPDRS-III “ON”] and cumulative Levodopa dose. Results PD patients had significantly reduced corneal nerve fiber density (CNFD) with increased corneal nerve branch density (CNBD) and corneal nerve fiber length (CNFL) compared to controls. CNBD and CNFL but not CNFD correlated inversely with UPDRS-III and SCOPA-AUT. All CCM parameters correlated strongly with DB-HRV. There was no correlation between CCM parameters and disease duration, cumulative Levodopa dose or pain. IENFD was significantly reduced in PD compared to controls and correlated with CNFD and UPDRS-III. However, unlike CCM measures, IENFD correlated with disease duration and cumulative Levodopa dose but not with autonomic dysfunction. Conclusion CCM identifies corneal nerve fiber pathology, which correlates with autonomic symptoms, parasympathetic deficits and motor scores in patients with PD. IENFD is also reduced and correlates with CNFD and motor symptoms but not parasympathetic deficits, indicating it detects different aspects of peripheral nerve pathology in PD. PMID:26578039
Chang, Wei-Yao; Chen, Kun-Huang; Chen, Der-Chin; Tseng, Jung-Kai; Chen, Shyan-Tarng; Sun, Han-Ying; Chen, Jing-Heng; Hsu, Ken Y.
This study proposes an accurate method for reconstructing the corneal surface profile. By applying a constant velocity to the projection grating along the grating plane, a series of sampling points of the sinusoidal wave, which behaves in the manner of heterodyne interferometric signals, can be recorded using a CMOS camera. The phase distribution of the moiré fringes can then be obtained using the IEEE 1241 least-square sine fitting algorithm and two-dimensional (2D) phase unwrapping. Finally, the corneal surface profile can be reconstructed by substituting the phase distribution into a specially derived equation. To validate the proposed method, the corneal surface of a pig eyeball was measured. The measurement resolution was approximately 3.5 μm. Because of the introduction of the Talbot effect, the projection moiré method, and heterodyne interferometry, this approach provides the advantages of a simple optical setup, ease of operation, high stability, and high resolution.
Pattmöller, Johanna; Wang, Jiong; Zemova, Elena; Seitz, Berthold; Eppig, Timo; Langenbucher, Achim; Szentmáry, Nóra
To analyze corneal surface temperature profile in a young and healthy study population and to determine the impact of corneal thickness (CT), anterior chamber depth (ACD), and endothelial cell density (ECD) on surface temperature. In this prospective, single-center study 61 healthy right eyes of 61 subjects without tear film pathologies (mean age 24.9 ± 6.7 years) were recruited. Ocular surface temperature (OST) was measured with the Ocular Surface Thermographer TG-1000. From Pentacam HR CT and ACD, and from specular microscopy ECD and central corneal thickness (CCT) were acquired. From the raw measurement data (OST, CT and ACD) we extracted a) local OST the corneal center and 3mm away from the center at the 3, 6, and 9 o'clock positions, and b) Zernike parameters Z1, Z2 and Z3 to evaluate the general temperature profile within a 6mm circular area around the center. Overall, there was no correlation between OST and CT, ACD or ECD. Local OST did not correlate with CT at any measurement position. On average local OST was highest at measurement positions where CT was lowest, but without reaching statistical significance. Baseline OST was highest at thin corneal regions and temperature decay over time was smallest in those regions. Z1, Z2 and Z3 correlated well with CT. In healthy subjects corneal thickness, endothelial cell density and anterior chamber depth have no effect on corneal surface temperature. The general temperature profile seems to be influenced by the corneal thickness profile effecting a higher temperature and lower decay at thinner corneal regions. Copyright © 2014. Published by Elsevier GmbH.
Bouazizi, Hala; Brunette, Isabelle; Meunier, Jean
Corneal topography is a medical imaging technique to get the 3D shape of the cornea as a set of 3D points of its anterior and posterior surfaces. From these data, topographic maps can be derived to assist the ophthalmologist in the diagnosis of disorders. In this paper, we compare three different mathematical parametric representations of the corneal surfaces leastsquares fitted to the data provided by corneal topography. The parameters obtained from these models reduce the dimensionality of the data from several thousand 3D points to only a few parameters and could eventually be useful for diagnosis, biometry, implant design etc. The first representation is based on Zernike polynomials that are commonly used in optics. A variant of these polynomials, named Bhatia-Wolf will also be investigated. These two sets of polynomials are defined over a circular domain which is convenient to model the elevation (height) of the corneal surface. The third representation uses Spherical Harmonics that are particularly well suited for nearly-spherical object modeling, which is the case for cornea. We compared the three methods using the following three criteria: the root-mean-square error (RMSE), the number of parameters and the visual accuracy of the reconstructed topographic maps. A large dataset of more than 2000 corneal topographies was used. Our results showed that Spherical Harmonics were superior with a RMSE mean lower than 2.5 microns with 36 coefficients (order 5) for normal corneas and lower than 5 microns for two diseases affecting the corneal shapes: keratoconus and Fuchs' dystrophy.
Ooi, E H; Ng, E Y K; Purslow, C; Acharya, R
This paper presents the two-dimensional simulation of heat propagation in the human eye model during contact lens wear with finite element analysis. Three types of contact lens are studied: Lotrafilcon A, Balafilcon A, and Etafilcon A. The models are solved for both steady and transient solutions. The corneal surface temperature during contact lens wear is found to decrease (average, 0.52 +/- 0.05 degrees C compared with a bare cornea for all lens types). A contact lens with a higher water content has a lower steady state temperature than a contact lens with a lower water content does. Various initial temperatures for the contact lens are found to affect the first 400 s of the temperature variation. When the initial temperature is lower than the corneal temperature, a reduction in temperature is observed during contact lens insertion while the opposite is observed when the initial temperature is higher than the corneal temperature. The increase in evaporation rate when a contact lens is worn increases the cooling effect on the ocular surface. This is suggested to be the cause of lower corneal surface temperature when wearing a contact lens.
Meeney, A; Mudhar, H S
The advanced specialist diploma in ophthalmic pathology was jointly ratified by the Royal College of Pathologists and the Institute of Biomedical Science in 2008. It results in extended roles for suitably qualified Biomedical Scientists (BMSs) in ophthalmic pathology specimen dissection and histological reporting of selected specimens, specifically non-neoplastic corneas. This study aimed to examine the reporting of corneal histology by a BMS training towards this diploma in comparison with a Consultant Ophthalmic Pathologist. This report covers a non-interventional, prospective examination of BMS's diagnostic skills. After 6 months training, 50 consecutive corneal cases were reported by the BMS and the same case reported by the consultant ophthalmic pathologist. The BMS's diagnosis was compared with the final consultant's diagnosis. This exercise was then repeated after 24 months of training. After 6 months, the BMS's diagnoses matched the consultant diagnoses in 44/50 (88%) cases. After 24 months, the BMS's diagnoses matched the consultant diagnoses in 48/50 (96%) of cases. The results indicate that BMS's reporting of corneal histology is a real and safe possibility. Furthermore, it indicated deficiencies in BMS's diagnostic skills to inform further training/knowledge acquisition.
Yáñez-Soto, Bernardo; Leonard, Brian C.; Raghunathan, Vijay Krishna; Abbott, Nicholas L.; Murphy, Christopher J.
Purpose The purpose of this study was to determine the influence of mucin expression in an immortalized human corneal epithelial cell line (hTCEpi) on the surface properties of cells, such as wettability, contact angle, and surface heterogeneity. Methods hTCEpi cells were cultured to confluence in serum-free medium. The medium was then replaced by stratification medium to induce mucin biosynthesis. The mucin expression profile was analyzed using quantitative PCR and Western blotting. Contact angles were measured using a two-immiscible liquid method, and contact angle hysteresis was evaluated by tilting the apparatus and recording advancing and receding contact angles. The spatial distribution of mucins was evaluated with fluorescently labeled lectin. Results hTCEpi cells expressed the three main ocular mucins (MUC1, MUC4, and MUC16) with a maximum between days 1 and 3 of the stratification process. Upon stratification, cells caused a very significant increase in contact angle hysteresis, suggesting the development of spatially discrete and heterogeneously distributed surface features, defined by topography and/or chemical functionality. Although atomic force microscopy measurements showed no formation of appreciable topographic features on the surface of the cells, we observed a significant increase in surface chemical heterogeneity. Conclusions The surface chemical heterogeneity of the corneal epithelium may influence the dynamic behavior of tear film by “pinning” the contact line between the cellular surface and aqueous tear film. Engineering the surface properties of corneal epithelium could potentially lead to novel treatments in dry eye disease. PMID:26747762
Krueger, R R; Campos, M; Wang, X W; Lee, M; McDonnell, P J
To compare the effects of blowing dry (nitrogen or helium) and humidified gases over the corneal surface during photorefractive keratectomy. Excimer laser myopic ablations were performed on porcine eyes (10 per group) using humidified and dry nitrogen and helium gas under ambient conditions. Surface smoothness was quantified with light and electron microscopy. Corneas that were ablated using humidified gas were smooth and equivalent to those ablated under ambient conditions. Dry nitrogen and helium blowing resulted in increased surface irregularity evident on light and electron microscopy (P < .001). The pseudomembranes in the humidified gas and ambient air groups had fewer surface discontinuities than did those in the nonhumdified gas groups and appeared to have a thinner electron-dense surface layer. The blowing of humidified gas during excimer laser corneal ablation produces a smoother surface than does the blowing of dry gas and is comparable to that produced under ambient (no blowing) conditions. Maintaining corneal moisture is important in photorefractive keratectomy. If blowing gas is necessary to remove debris from the surface, the gas should be humidified.
Latour, Gaël; Georges, Gaëlle; Lamoine, Laure Siozade; Deumié, Carole; Conrath, John; Hoffart, Louis
The cornea is the only transparent tissue in the body. The transparency is the main characteristic of the corneal tissue, and depends not only on the transmission coefficient but also on the losses by scattering and absorption. The scattering properties of the cornea tissues become one of the most important parameters in the case of the corneal graft. These scattering properties are studied in this paper in the reflected half area, similar to the diagnosis configuration. We quantify the influence of the cornea thickness and of the epithelial layer on scattering level. The technique of ellipsometry on scattered field is also used to analyze the polarization properties in order to determine the origin of scattering (surface and/or bulk).
Sarayba, Melvin A; Tungsiripat, Tulaya; Sweet, Paula M; Chuck, Roy S
A portable, gas-driven turbine microkeratome device capable of harvesting the entire anterior corneal surface for lamellar transplantation on human donor globes was evaluated. The device consisted of a modified LASIK microkeratome with an enlarged suction ring, head, and blade. Vacuum was achieved by a simple hand pump. Lamellar keratectomy was performed on 5 fresh human donor globes. Lenticule dimensions were measured on days 0, 3, 6, and 9 after storage in preservation media at 4 degrees C. On day 0, the obtained lenticules were 13.9 +/- 0.9 mm and 13.5 +/- 0.4 mm, vertical and horizontal diameters, respectively. The average central lenticule thickness was 152.2 +/- 52 microm. Each lenticule was uniform in thickness over 5 measurement points (P = 0.74). Repeat measurements of corneal thickness over the 9 days showed no statistically significant difference (P = 0.51). On day 9 lenticules were 14.6 +/- 0.3 mm and 14.6 +/- 0.4 mm, vertical and horizontal diameters, respectively. When day 0 was compared to day 9, vertical diameter also showed no statistically significant difference (P = 0.16), whereas horizontal diameter was significantly different (P < 0.001). This device proves to be an economical alternative to electric-powered systems for the harvest of transplantable corneal sections.
Although comparison phakometry has been used by a number of studies to measure posterior corneal shape, these studies have not calculated the size of the posterior corneal zones of reflection they assessed. This paper develops paraxial equations for calculating posterior corneal zones of reflection, based on standard keratometry equations and equivalent mirror theory. For targets used in previous studies, posterior corneal reflection zone sizes were calculated using paraxial equations and using exact ray tracing, assuming spherical and aspheric corneal surfaces. Paraxial methods and exact ray tracing methods give similar estimates for reflection zone sizes less than 2 mm, but for larger zone sizes ray tracing methods should be used.
Chaurasia, Shyam S.; Lim, Rayne R.; Lakshminarayanan, Rajamani; Mohan, Rajiv R.
Corneal diseases are the third leading cause of blindness globally. Topical nonsteroidal anti-inflammatory drugs (NSAIDs), steroids, antibiotics and tissue transplantation are currently used to treat corneal pathological conditions. However, barrier properties of the ocular surface necessitate high concentration of the drugs applied in the eye repeatedly. This often results in poor efficacy and several side-effects. Nanoparticle-based molecular medicine seeks to overcome these limitations by enhancing the permeability and pharmacological properties of the drugs. The promise of nanomedicine approaches for treating corneal defects and restoring vision without side effects in preclinical animal studies has been demonstrated. Numerous polymeric, metallic and hybrid nanoparticles capable of transporting genes into desired corneal cells to intercept pathologic pathways and processes leading to blindness have been identified. This review provides an overview of corneal diseases, nanovector properties and their applications in drug-delivery and corneal disease management. PMID:25941990
Papaioannou, Thanassis; Maguen, Ezra I.; Grundfest, Warren S.
Accurate prediction of LTK treatments requires refined thermal corneal models which necessitate precise input parameters. The overall objective of this study was to provide detailed information on the spatiotemporal temperature profile of the corneal surface, during in-vitro thermal keratoplasty. LTK was performed in-vitro on freshly harvested porcine eyes (N equals 16) with the Sunrise Technologies corneal shaping system (Model SUN 1000). Spatiotemporal thermal imaging of the irradiated corneas were obtained with a short wave Inframetrics thermal camera (Model PM290). Images were obtained at 8-bits resolution, with ~100 microns spatial and ~17 msec temporal resolution respectively. Treatment pattern consisted of eight spots at 6 mm zone, while lasing was conducted at settings of either 100 mJ and 15 pulses (N equals 8), or 260 mJ and 7 pulses (N equals 8). Temporal and spatial variation of the corneal surface temperatures were calculated at locations of importance to LTK. At the laser spot, temperature profiles consisted of transients coinciding approximately with the laser pulses. Maximum transient temperatures observed were 98.0+/- 4.6 degree(s)C for the high and 56.3+/- 2.6 degree(s)C for the low energy respectively. These temperature transients were superimposed on an envelope of lower-slowly varying temperatures. The maximum temperatures observed for this temperature envelope, were 51.8+/- 3.4 degree(s)C for the high and 35.4+/- 3.4 degree(s)C for the low energy respectively. The evolution of either the maximum temperature transients or the lower temperature envelope, followed exponential growth of the form: T equals A * exp(B*t). Maximum temperatures at locations 0.5 mm and 1 mm away from the laser spot, reached 25.7 degree(s)C and 23.3 degree(s)C for the low energy, and 34 degree(s)C and 25.6 degree(s)C for the high energy settings respectively. Temperature decay constants were approximately 2 to 3 sec, while the spatial temperature profile at the laser
Cheng, Anny M. S.; Chua, Lorraine; Casas, Victoria; Tseng, Scheffer C. G.
Purpose To evaluate the clinical efficacy of morselized amniotic membrane and umbilical cord tissue (MAU) in treating refractory corneal epithelial defect in ocular cicatricial diseases. Methods Retrospective review of four patients with ocular cicatricial diseases treated with topical MAU for corneal epithelial defects refractory to conventional treatments including topical lubricants, autologous serum, bandage contact lens, and tarsorraphy. Their symptoms, corneal staining, conjunctival inflammation, and visual acuity were compared before and after treatment. Results After topical application of MAU twice daily, two patients demonstrated rapid corneal epithelialization with prompt visual acuity improvement at the first day. All patients showed corneal epithelialization in 7.3 ± 2.6 days accompanied by a significant relief of symptoms, reduction of ocular surface inflammation, and improvement of visual acuity. Conclusion This pilot study suggests topical MAU can be developed into a novel treatment for treating refractory corneal epithelial defects. Translational Relevance Topical MAU can be an effective novel treatment for refractory corneal epithelial defects. PMID:27226933
Le, Ryan; Yucel, Narain; Khattak, Shireen; Yucel, Yeni H; Prud'homme, Gerald J; Gupta, Neeru
To determine the most common reasons and surgical approaches for corneal graft surgery at the Kensington Eye Institute (KEI), University of Toronto. Retrospective cross-sectional study. A total of 229 consecutive corneal transplants performed at the KEI. Demographic, clinical, and pathological data on all 2012 and 2013 corneal transplants were collected. The mean age for corneal transplants was 65 ± 16 years; 39% were full-thickness penetrating keratoplasties (PK) and 61% were partial-thickness. Graft failure (30%), infection (18%), and keratoconus (17%) were the leading indications for PK. Fuchs' dystrophy (40%) and bullous keratopathy (24%) were main causes for partial-thickness procedures. Among partial-thickness approaches, Descemet's stripping automated endothelial keratoplasty (DSAEK), deep anterior lamellar keratoplasty (DALK), and Descemet's membrane endothelial keratoplasty (DMEK) procedures accounted for 68%, 16%, and 16%, respectively. Fuchs' dystrophy (40%) and bullous keratopathy (33%) were the most common indications for DSAEK. Keratoconus (57%) and corneal scarring (35%) were the most common indications for DALK, whereas Fuchs' dystrophy (82%) accounted for most DMEK procedures. The most common reasons for all corneal grafts were Fuchs' dystrophy (25%), bullous keratopathy (21%), graft failure (17%), and keratoconus (12%). Almost two-thirds of all corneal transplant procedures at the University of Toronto are partial thickness procedures. A failed graft was found to be the most common indication for full-thickness transplants. Fuchs' dystrophy was the most common indication for a partial-thickness approach, most often treated by DSAEK. Longitudinal data are needed to determine whether partial-thickness surgeries will improve graft survival and reduce the need for regraft. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.
Klamann, Matthias K J; Maier, Anna-Karina B; Gonnermann, Johannes; Klein, Julian Philip; Bertelmann, Eckart; Pleyer, Uwe
To investigate the ocular surface temperature gradient in eyes with bacterial corneal ulcers. Prospective examination of 12 eyes with bacterial corneal ulcers (group 1) and 12 control eyes (group 2). Infrared thermal imaging (Tomey TG 1000) was used to study the temperature of the ocular surface. The mean, minimum and maximum temperature of the ocular surface and temperature course over a time period of 10 s of sustained eye opening were evaluated. Furthermore, a correlation between the overall corneal temperature and the temperature at the base of the corneal ulcers was determined. A significant difference between both groups was present. Mean corneal temperature was 35.6°C ± 0.9 in group 1 and 34.8°C ± 0.8 in group 2 (p = 0.033). The temperature course over 10 s of sustained eye opening was -0.6°C ± 0.4 in group 1 and -0.3°C ± 0.2 in group 2 (p = 0.045). There was a close correlation between the mean temperature at the base of the corneal ulcer and the overall corneal temperature (r = 0.92, p < 0.001). Infrared thermal imaging can be used to objectively determine the increased ocular surface temperature in patients with bacterial corneal ulcers. The use of dynamic thermography may offer new options to monitor ocular surface alterations. Copyright © 2012 S. Karger AG, Basel.
Posch, Leila C.; Zhu, Meifang; Robertson, Danielle M.
Purpose. To evaluate the effects of a chemically preserved multipurpose contact lens care solution (MPS) on the corneal epithelial surface and Pseudomonas aeruginosa (PA) internalization in the rabbit corneal epithelium. Methods. Rabbits were fit in one eye with a silicone hydrogel lens (balafilcon A) soaked overnight in a borate-buffered MPS (BioTrue). The contralateral eye was fit with a lens removed directly from the blister pack containing borate-buffered saline (control). Lenses were worn for 2 hours. Upon lens removal, corneas were challenged ex vivo with invasive PA strain 6487 and assessed for PA internalization. Ultrastructural changes were assessed using scanning electron (SEM) and transmission electron microscopy (TEM). Results. Scanning electron microscopy showed frank loss of surface epithelium in MPS-exposed eyes, while control eyes exhibited occasional loss of surface membranes but retention of intact junctional borders. Transmission electron microscopy data supported and extended SEM findings, demonstrating the presence of epithelial edema in MPS-treated eyes. There was a 12-fold increase in PA uptake into the corneal epithelium following wear of the MPS-treated lens compared to control (P = 0.008). Conclusions. These data demonstrate that corneal exposure to MPS during lens wear damages the surface epithelium and are consistent with our previous clinical data showing an increase in bacterial binding to exfoliated epithelial cells following MPS use with resultant increased risk for lens-mediated infection. These findings also demonstrate that the PA invasion assay may provide a highly sensitive quantitative metric for assessing the physiological impact of lens-solution biocompatibility on the corneal epithelium. PMID:24876286
Corneal epithelial abrasion elicits an inflammatory response involving neutrophil (PMN) recruitment from the limbal vessels into the corneal stroma. These migrating PMNs make surface contact with collagen and stromal keratocytes. Using mice deficient in PMN integrin CD18, we previously showed that P...
Di, Yue; Li, Mei-Yan; Qiao, Tong; Lu, Na
AIM To select the optimal edge detection methods to identify the corneal surface, and compare three fitting curve equations with Matlab software. METHODS Fifteen subjects were recruited. The corneal images from optical coherence tomography (OCT) were imported into Matlab software. Five edge detection methods (Canny, Log, Prewitt, Roberts, Sobel) were used to identify the corneal surface. Then two manual identifying methods (ginput and getpts) were applied to identify the edge coordinates respectively. The differences among these methods were compared. Binomial curve (y=Ax2+Bx+C), Polynomial curve [p(x)=p1xn+p2xn−1 +....+pnx+pn+1] and Conic section (Ax2+Bxy+Cy2+Dx+Ey+F=0) were used for curve fitting the corneal surface respectively. The relative merits among three fitting curves were analyzed. Finally, the eccentricity (e) obtained by corneal topography and conic section were compared with paired t-test. RESULTS Five edge detection algorithms all had continuous coordinates which indicated the edge of the corneal surface. The ordinates of manual identifying were close to the inside of the actual edges. Binomial curve was greatly affected by tilt angle. Polynomial curve was lack of geometrical properties and unstable. Conic section could calculate the tilted symmetry axis, eccentricity, circle center, etc. There were no significant differences between ‘e’ values by corneal topography and conic section (t=0.9143, P=0.3760 >0.05). CONCLUSION It is feasible to simulate the corneal surface with mathematical curve with Matlab software. Edge detection has better repeatability and higher efficiency. The manual identifying approach is an indispensable complement for detection. Polynomial and conic section are both the alternative methods for corneal curve fitting. Conic curve was the optimal choice based on the specific geometrical properties. PMID:28393021
Di, Yue; Li, Mei-Yan; Qiao, Tong; Lu, Na
To select the optimal edge detection methods to identify the corneal surface, and compare three fitting curve equations with Matlab software. Fifteen subjects were recruited. The corneal images from optical coherence tomography (OCT) were imported into Matlab software. Five edge detection methods (Canny, Log, Prewitt, Roberts, Sobel) were used to identify the corneal surface. Then two manual identifying methods (ginput and getpts) were applied to identify the edge coordinates respectively. The differences among these methods were compared. Binomial curve (y=Ax(2)+Bx+C), Polynomial curve [p(x)=p1x(n)+p2x(n-1) +....+pnx+pn+1] and Conic section (Ax(2)+Bxy+Cy(2)+Dx+Ey+F=0) were used for curve fitting the corneal surface respectively. The relative merits among three fitting curves were analyzed. Finally, the eccentricity (e) obtained by corneal topography and conic section were compared with paired t-test. Five edge detection algorithms all had continuous coordinates which indicated the edge of the corneal surface. The ordinates of manual identifying were close to the inside of the actual edges. Binomial curve was greatly affected by tilt angle. Polynomial curve was lack of geometrical properties and unstable. Conic section could calculate the tilted symmetry axis, eccentricity, circle center, etc. There were no significant differences between 'e' values by corneal topography and conic section (t=0.9143, P=0.3760 >0.05). It is feasible to simulate the corneal surface with mathematical curve with Matlab software. Edge detection has better repeatability and higher efficiency. The manual identifying approach is an indispensable complement for detection. Polynomial and conic section are both the alternative methods for corneal curve fitting. Conic curve was the optimal choice based on the specific geometrical properties.
Du, Juan; Liu, Rong-Qiang; Ye, Lei; Li, Zhi-Hui; Zhao, Feng-Tu; Jiang, Nan; Ye, Lin-Hong; Shao, Yi
AIM To determine typical corneal changes of congenital aniridic keratopathy (CAK) using corneal topography and confocal systems, and to identify characteristics that might assist in early diagnosis. METHODS Patients with CAK and healthy control subjects underwent detailed ophthalmic examinations including axial length, corneal thickness, tear film condition, corneal topography, and laser-scanning in vivo confocal microscopy (IVCM). RESULTS In early stage aniridic keratopathy, Schirmer I test (SIT), break-up time (BUT), mean keratometry (mean K) and simulated keratometry (sim K) were reduced relative to controls (P<0.05), while simulation of corneal astigmatism (sim A) and corneal thickness were increased (P<0.05). In addition, significantly more eyes exhibited flat cornea compared with the control group. Inflammatory dendritic cells were present in the aniridic epithelium, with significantly increased density relative to controls (P<0.05). Palisade ridge-like features and abnormal cell morphology were observed in six out of sixteen CAK cases. In central cornea area, the aniridic corneas had the increased subbasal nerve density. CONCLUSION These changes in corneal morphology in borderline situations can be useful to confirm the diagnosis of CAK. PMID:28393028
Salvetat, Maria L.; Zeppieri, Marco; Miani, Flavia; Brusini, Paolo
Purpose. To compare the higher-order aberrations (HOAs) due to the anterior and posterior corneal surfaces in patients that underwent either Descemet-stripping-automated-endothelial-keratoplasty (DSAEK) or penetrating keratoplasty (PK) for endothelial dysfunction and age-matched controls. Methods. This retrospective, observational, case series included 28 patients after PK, 30 patients after DSAEK, and 30 healthy controls. A Scheimpflug imaging system was used to assess the HOAs due to the anterior and posterior corneal surfaces at 4 mm and 6 mm optical zones. Total, 3rd and 4th order HOAs were considered. Intra- and intergroup differences were assessed using the Friedman and the Kruskal-Wallis tests, respectively; paired comparisons were performed using Duncan's multiple range test. Results. Total, 3rd and 4th order HOAs due to both corneal surfaces at 4 mm and 6 mm optical zones were significantly higher in the PK group, intermediate in the DSAEK group, and lower in controls (P < 0.05). The most important HOAs components in both PK and DSAEK groups were trefoil and coma from the anterior corneal surface (P < 0.05) and trefoil from the posterior corneal surface (P < 0.05). Conclusions. The optical quality of both corneal surfaces appeared significantly higher after DSAEK than after PK, which can increase the postoperative patient's quality of vision and satisfaction. PMID:24558599
Baumeister, M; Klaproth, O K; Gehmlich, J; Bühren, J; Kohnen, T
Collagen cross-linking with administration of riboflavin and UV radiation may delay or halt the progression of keratoconus. This study examines the effects of the treatment on the corneal wavefront error. Twenty eyes of 20 patients with keratoconus received collagen cross-linking with riboflavin administration and 30 min of UV radiation at a wavelength of 365 nm. Preoperatively as well as 1 and 6 months postoperatively, the corneal wavefront error was computed from axial keratometric topography data by Zernike decomposition over a pupil diameter of 6 mm. Preoperative mean keratometric astigmatism was 5.37 +/- 2.36 D. Six months postoperatively it was 5.29 +/- 2.73 D (p = 0.35). Total higher order aberrations were preoperatively 3.35 +/- 1.65 microm and after 6 months 3.31 +/- 1.79 microm (p = 0.116). Coma's root mean square was 2.94 +/- 1.47 microm preoperatively and 2.75 +/- 1.38 microm after 6 months (p = 0.047). Within the first 6 postoperative months, collagen cross-linking with riboflavin administration and UVA irradiation does not significantly increase or decrease corneal wavefront aberrations.
Kirkness, C M; McCartney, A; Rice, N S; Garner, A; Steele, A D
The clinical and histological features of congenital hereditary corneal oedema in 23 patients are presented. The series includes cases of both recessive and dominant inheritance. Although the condition is present at birth or in early childhood, visual development appears to be little impaired, if at all. Penetrating keratoplasty carries a relatively good surgical prognosis and can produce a substantial visual gain even when carried out late in life. Images PMID:3548808
McNutt, Patrick M; Tuznik, Kaylie M; Glotfelty, Elliot J; Nelson, Marian R; Lyman, Megan E; Hamilton, Tracey A
Corneal injuries resulting from ocular exposure to sulfur mustard (SM) vapor are the most prevalent chemical warfare injury. Ocular exposures exhibit three distinct, dose-dependent clinical trajectories: complete injury resolution, immediate transition to a chronic injury, or apparent recovery followed by the subsequent development of persistent ocular manifestations. These latter two trajectories include a constellation of corneal symptoms that are collectively known as mustard gas keratopathy (MGK). The etiology of MGK is not understood. Here, we synthesize recent findings from in vivo rabbit SM vapor studies, suggesting that tissue-specific damage during the acute injury can decrement the regenerative capacities of corneal endothelium and limbal stem cells, thereby predisposing the cornea to the chronic or delayed forms of MGK. This hypothesis not only provides a mechanism to explain the acute and MGK injuries but also identifies novel therapeutic modalities to mitigate or eliminate the acute and long-term consequences of ocular exposure to SM vapor. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.
Schneider, Martin; Iskander, D Robert; Collins, Michael J
High-speed videokeratoscopy is an emerging technique that enables study of the corneal surface and tear-film dynamics. Unlike its static predecessor, this new technique results in a very large amount of digital data for which storage needs become significant. We aimed to design a compression technique that would use mathematical functions to parsimoniously fit corneal surface data with a minimum number of coefficients. Since the Zernike polynomial functions that have been traditionally used for modeling corneal surfaces may not necessarily correctly represent given corneal surface data in terms of its optical performance, we introduced the concept of Zernike polynomial-based rational functions. Modeling optimality criteria were employed in terms of both the rms surface error as well as the point spread function cross-correlation. The parameters of approximations were estimated using a nonlinear least-squares procedure based on the Levenberg-Marquardt algorithm. A large number of retrospective videokeratoscopic measurements were used to evaluate the performance of the proposed rational-function-based modeling approach. The results indicate that the rational functions almost always outperform the traditional Zernike polynomial approximations with the same number of coefficients.
Kitazawa, Koji; Yokota, Isao; Sotozono, Chie; Kinoshita, Shigeru
To calculate the number of corneal endothelial cells (CEC) on the posterior surface of the normal human cornea by measuring specific surface areas through anterior segment optical coherence tomography. The effects of age, sex, and variations between the right and left eyes were also investigated. This study involved 60 eyes of 30 normal subjects with no history of corneal disease. Subjects were divided into the following groups according to age: group A (20-39 years old), group B (40-59 years old), and group C (60-79 years old). Set areas of the corneal posterior surface were imaged and analyzed using anterior segment optical coherence tomography, and the number of CECs was calculated based on the area measured and a CEC density. The posterior corneal surface area measured within the central circular diameters of 10.2, 8.5, and 7.5 mm was 86.8, 63.8, and 48.4 mm in group A, 86.0, 63.8, and 48.4 mm in group B, and 87.0, 64.2, and 48.6 mm in group C, respectively. The total number of CECs on the posterior surface in the diameters of 10.2, 8.5, and 7.5 mm was 2.3 × 10, 1.7 × 10, and 1.3 × 10, respectively. No clinically relevant differences in the posterior surface were found in relation to age, sex, or variation between right and left eyes. Calculation of the CEC number on the corneal posterior surface is essential for determining the number of cells applied during penetrating keratoplasty, endothelial keratoplasty, or cultivated CEC injection therapy when available.
Gasymov, Oktay K; Abduragimov, Adil R; Prasher, Pawan; Yusifov, Taleh N; Glasgow, Ben J
Lipid contamination of the cornea may create an unwettable surface and result in desiccation of the corneal epithelium. Tear lipocalin (TL), also known as lipocalin-1, is the principal lipid-binding protein in tears. TL has been shown to scavenge lipids from hydrophobic surfaces. The hypothesis that TL can remove contaminating fatty acids and phospholipids from the human corneal surface was tested. TL was purified from pooled human tear samples by size exclusion and ion exchange chromatographies. Tears depleted of TL were reconstituted from fractions eluted by size exclusion chromatography that did not contain TL. Fresh and formalin-fixed human corneas were obtained from exenteration specimens. Fluorescent analogs of either palmitic acid or phosphatidylcholine were applied to the corneal epithelial surface. Tears, TL, or tears depleted of TL were applied over the corneas, and spectrofluorometry and fluorescent stereomicroscopy were used to monitor the removal of fluorescent lipids. Tears used in the experiments were then fractionated by size exclusion chromatography to determine the component of tears associated with fluorescent lipids. Significant enhancement of fluorescence for 16AP and NBD C(6)-HPC was evident in solutions incubated with whole tears and purified TL but not with tears depleted of TL for fixed and unfixed corneas. After the experiment, size exclusion fractions of tears showed that the fluorescence component coeluted with TL. TL scavenges lipids from the human corneal surface and delivers them into the aqueous phase of tears. TL may have an important role in removing lipids from the corneal surface to maintain the wettability and integrity of the ocular surface.
Wojtkowski, M.; Kałużny, B.; Szkulmowska, A.; Bajraszewski, T.; Szkulmowski, M.; Targowski, P.; Kowalczyk, A.
Purpose: To show potential of Spectral Optical Coherence Tomography system for high resolution, cross-sectional and three-dimensional imaging of eye surface pathologies. Methods: High-speed spectral OCT prototype instrument with 4.5 μm axial resolution was designed and constructed for clinical use. Measurements of anterior segment of human eye have been performed in ophthalmology clinic on 86 patients suffering various eye surface disorders including corneal dystrophies, corneal scars, conjunctival folds, keratoconus, bullus keratopathy, filtration blebs and other post-operative changes. Additionally, examinations of contact lens fit on 97 healthy corneas have been performed up to date. Results: High quality, high resolution cross-sectional images and three-dimensional reconstructions of cornea, conjunctiva and sclera of pathologic eyes together with examples of numerical analysis including segmentation of fluid in filtration blebs, scars and deposits are shown. Quantitative analysis of contact lens fit is demonstrated.
Brenner, Luis F; Renna, Antonio; Pandolfi, Anna; Cavas-Martinez, Francisco; Alió, Jorge L
To evaluate refractive results and the theoretical elastic response of photorefractive keratectomy in eyes with asymmetrical corneal surface and to compare such outcomes with a control-matched group of normal topographies. Retrospective interventional case series with matched comparison group. Thirty eyes with superior-inferior dioptric difference (SI index) > 1.40 diopter (D) were compared to 30 eyes with normal topographies. Both groups were matched for age, preoperative spherical equivalent (SE), mean keratometry, and percentage of tissue altered (PTA). Refractive results and the theoretical elastic modulus calculations were evaluated. The mean preoperative SI index in the asymmetrical group was 2.06 ± 0.56 D vs 0.14 ± 0.73 D in the control group (P < .001). From 3 to 12 months postoperatively, the asymmetrical group presented a mean re-steepening of 0.51 ± 0.39 D vs 0.19 ± 0.40 D in the control group (P = .014). The mean PTA of 14.42% generated a theoretical elastic modulus reduction of 10.25% in the asymmetrical group vs 2.45% in the control group (P = .006). The reduction of the theoretical elastic modulus correlated with the preoperative SI index (ρ = -0.387, P = .007). After 36 months, 90% of all eyes were within ±0.50 D of SE and the theoretical elastic modulus did not present a significant difference between both groups (P = .085). Asymmetrical-topography corneas treated with myopic surface ablation presented an increased short-term keratometric re-steepening and reduction of the theoretical elastic moduli. The long-term follow-up indicated that, in selected cases of asymmetrical topographies, myopic surface ablation could induce a premature biomechanical elastic response rather than a progressive pathologic process. Copyright © 2017 Elsevier Inc. All rights reserved.
Preussner, Paul-Rolf; Hoffmann, Peter; Wahl, Jochen
To quantify the impact of posterior cornea on toric IOL calculation accuracy using Placido-topography of anterior corneal surface and Scheimpflug measurements of corneal thickness. Three-hundred seventy-nine non-selected eyes undergoing cataract surgery with non-toric intraocular lens (IOL) implantation were measured with TMS-5 (Tomey, Japan), IOLMaster (Zeiss, Germany) and Lenstar (Haag-Streit, Switzerland). Anterior, posterior and total measured corneal astigmatisms were compared with astigmatisms from postoperative refraction by calculating vector differences. The average absolute vector difference between anterior astigmatism and total astigmatism combining the measurements of anterior and posterior cornea was only 0.3 ± 0.2 D, with a median of only 0.27 D, but a maximum of 1.5 D. Measurements of anterior cornea alone show a systematic difference from refractive cylinder of 0.3-6 D at 90, 0.38 D at 89° and 0.28 D at 91° (IOLMaster, Lenstar and anterior TMS5), whereas the total TMS5 cylinder differs on average by only 0.14D at 81° from the refractive cylinder. With-the-rule (WTR) corneal astigmatism is slightly reduced and against-the-rule (ATR) astigmatism slightly increased on average when posterior corneal surface is taken into account additionally. This could also be confirmed by the calculation of an average pachymetry of all eyes in which the thinnest central part shows an ellipsoidal shape with horizontally long axis. Measurements of posterior cornea have on average only a small but significant impact on the outcome of toric IOL calculation, however, they are nevertheless recommended to detect outliers in which corneal irregularities (e.g. beginning keratokonus) may be overlooked.
Corneal epithelial abrasion is associated with an inflammatory response that involves PMN recruitment from the limbal vessels into the corneal stroma. Previously, in the injured mouse cornea, we showed that migrating PMNs not only make contact with collagen, but they also make extensive surface cont...
Gagen, Debjani; Laubinger, Sara; Li, Zhijie; Petrescu, Matei S.; Brown, Evelyn S.; Smith, C. Wayne; Burns, Alan R.
Corneal epithelial abrasion elicits an inflammatory response involving neutrophil (PMN) recruitment from the limbal vessels into the corneal stroma. These migrating PMNs make surface contact with collagen and stromal keratocytes. Using mice deficient in PMN integrin CD18, we previously showed that PMN contact with stromal keratocytes is CD18-dependent, while contact with collagen is CD18-independent. In the present study, we wished to extend these observations and determine if ICAM-1, a known ligand for CD18, mediates PMN contact with keratocytes during corneal wound healing. Uninjured and injured right corneas from C57Bl/6 wild type (WT) mice and ICAM-1−/− mice were processed for transmission electron microscopy and imaged for morphometric analysis. PMN migration, stromal thickness, and ICAM-1 staining were evaluated using light microscopy. Twelve hours after epithelial abrasion, PMN surface contact with paralimbal keratocytes in ICAM-1−/− corneas was reduced to ~50% of that observed in WT corneas; PMN surface contact with collagen was not affected. Stromal thickness (edema), keratocyte network surface area and keratocyte shape were similar in ICAM-1−/− and WT corneas. WT keratocyte ICAM-1 expression was detected at baseline and ICAM-1 staining intensity increased following injury. Since ICAM-1 is readily detected on mouse keratocytes and PMN-keratocyte surface contact in ICAM-1−/− mice is markedly reduced, the data suggest PMN adhesive interactions with keratocyte stromal networks is in part regulated by keratocyte ICAM-1 expression. PMID:20713042
Nanji, Afshan A.; Sayyad, Fouad E.; Galor, Anat; Dubovy, Sander; Karp, Carol L
Purpose To evaluate the use of a commercially-available, high-resolution, spectral-domain optical coherence tomography (HR OCT) device in the diagnosis of corneal and conjunctival pathologies, with a focus on malignant lesions. Methods Eighty-two eyes of 71 patients were enrolled in this prospective case series, including 10 normal eyes, 21 with ocular surface squamous neoplasia (OSSN), 24 with a pterygium or pingueculum, 3 with lymphoma, 18 with pigmented conjunctival lesions (nevus, flat melanosis, or melanoma), and 6 with Salzmann’s nodular degeneration. Subjects were imaged using photography and HR OCT (RTVue, Optovue, Fremont, CA). When clinically indicated, surgery was performed and histopathologic specimens were correlated with OCT images. Results HR OCT was useful in differentiating among various lesions based on optical signs. Specifically, in OSSN, HR OCT findings included epithelial thickening and hyper-reflectivity, whereas pterygia and pinguecula showed a subepithelial mass under thinner epithelium. In lymphoma, a hypo-reflective, homogenous subepithelial mass was observed. Differentiating between pigmented lesions with HR OCT proved more difficult, but certain characteristics could be identified. Eyes with nevi and melanoma both displayed intensely hyper-reflective basal epithelial layers and discrete subepithelial lesions, but could be differentiated by the presence of cysts in nevi and intense shadowing of sublesional tissue in most melanomas. Conclusion We found that a commercially-available HR OCT was a useful non-invasive adjunctive tool in the diagnosis of ocular surface lesions. PMID:26045235
Lyubovitsky, Julia G.; Spencer, Joel A.; Krasieva, Tatiana B.; Andersen, Bogi; Tromberg, Bruce J.
A transgenic mouse model with a Clim [co-factor of LIM (a combination of first letters of Lin-11 (C. elegans), ISL1 (rat), and Mec-3 (C. elegans) gene names) domain proteins] gene partially blocked in the epithelial compartment of its tissues is used to establish the sensitivity of intrinsic reflectance nonlinear optical microscopy (NLOM) to stromal and cellular perturbations in the cornea. Our results indicate dysplasia in the squamous epithelium, irregular collagen arrays in the stroma, and a compromised posterior endothelium in the corneas of these mice. As suggested by biochemical data, the collagen alterations are likely due to collagen III synthesis and deposition during healing and remodeling of transgenic mice corneal stromas. All of the topographic features seen in NLOM images of normal and aberrant corneas are confirmed by coregistration with histological sections. In this work, we also use ratiometric redox fluorometry based on two-photon excited cellular fluorescence from reduced nicotinamide adenine dinucleotide (NAD)(P)H and oxidized flavin adenine dinucleotide (FAD) to study mitocondrial energy metabolism. Employing this method, we detect higher metabolic activity in the endothelial layer of cornea compared to an epithelial layer located further away from the metabolites. The combination of two-photon excited fluorescence (TPF) with second harmonic generation (SHG) signals allows imaging to aid in understanding the relationship between alternation of specific genes and structural changes in cells and extracellular matrix.
Ma, Yanling; Xu, Yongsheng; Xiao, Zhifeng; Yang, Wei; Zhang, Chun; Song, E; Du, Yiqin; Li, Lingsong
To examine whether transplantation of human mesenchymal stem cells (MSCs) could reconstruct the corneal damage and also whether grafted MSCs could differentiate into corneal epithelial cells, we isolated MSCs from healthy donors. After growth and expansion on amniotic membrane, cells were transplanted into rat corneas 7 days after chemical burns. Reconstruction of the damaged cornea and the rat vision were measured once a week by slit lamp and by an optokinetic head-tracking instrument, respectively. Corneas were then cut out, fixed, and imbedded for immunofluorescent study of the expression of keratin 3 and keratin-pan as epithelial cell markers. Expression of CD45, interleukin 2, and metalloproteinase-2 was also investigated for inflammation and inflammation-related angiogenesis. The data showed that transplantation of MSCs, like limbal epithelial stem cells, successfully reconstructed damaged rat corneal surface. Interestingly, the therapeutic effect of the transplantation may be associated with the inhibition of inflammation and angiogenesis after transplantation of MSCs rather than the epithelial differentiation from MSCs. This study provides the first line of evidence that MSCs can be used for reconstruction of damaged corneas, presenting a new source for autotransplantation in the treatment of corneal disorders.
Collin, H B; Collin, S P
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
Swamynathan, Sudha; Delp, Emili E.; Harvey, Stephen A. K.; Loughner, Chelsea L.; Raju, Leela; Swamynathan, Shivalingappa K.
Purpose Although secreted Ly6/urokinase-type plasminogen activator receptor–related protein-1 (Slurp1) transcript is highly abundant in the mouse cornea, corresponding protein expression remains uncharacterized. Also, SLURP1 was undetected in previous tear proteomics studies, resulting in ambiguity about its baseline levels. Here, we examine mouse corneal Slurp1 expression in different sexes, age groups, strains, and health conditions, and quantify SLURP1 in human tears from healthy or inflamed ocular surfaces. Methods Expression of Slurp1 in embryonic day-13 (E13), E16, postnatal day-1 (PN1), PN10, PN20, and PN70 Balb/C, FVBN, C57Bl/6, and DBA/2J mouse corneas, Klf4Δ/ΔCE corneas with corneal epithelial–specific ablation of Klf4, migrating cells in wild-type corneal epithelial wound edge, and in corneas exposed to pathogen-associated molecular patterns (PAMPs) poly(I:C), zymosan-A, or Pam3Csk4 was examined by QPCR, immunoblots, and immunofluorescent staining. Human SLURP1 levels were quantified by ELISA in tears from 34 men and women aged 18 to 80 years. Results Expression of Slurp1, comparable in different strains and sexes, was low in E13, E16, PN1, and PN10 mouse corneas, and increased rapidly after eyelid opening in a Klf4-dependent manner. We found Slurp1 was downregulated in corneas exposed to PAMPs, and in migrating cells at the wound edge. Human SLURP1 expression, comparable in different sexes and age groups, was significantly decreased in tears from inflamed ocular surfaces (0.34%) than those from healthy individuals (0.77%). Conclusions These data describe the influence of age, sex, genetic background, and ocular surface health on mouse corneal expression of Slurp1, establish the baseline for human tear SLURP1 expression, and identify SLURP1 as a useful diagnostic and/or therapeutic target for inflammatory ocular surface disorders. PMID:26670825
Tonn, Bastian; Klaproth, Oliver Klaus; Kohnen, Thomas
Description of total corneal refractive power (TCRP) astigmatism by ray tracing using a Scheimpflug tomographer. Analysis of Scheimpflug tomography measurements to determine 3-mm-zone TCRP astigmatism (CATCRP) by ray tracing calculations, astigmatism in 15°-zone from simulated keratometry (CASim-K), anterior-surface astigmatism (CAant), and posterior-surface astigmatism (CApost). An analysis of changes with age was performed. The error produced by estimating CATCRP using CASim-K was calculated through vector analyses. The percentages of steep meridian aligned vertically, obliquely, and horizontally of CAant and CApost were calculated. A total of 3818 healthy, previously unoperated eyes were analyzed. The mean magnitude of CApost was -0.33 diopter (D). A vertically aligned steep meridian (60° to 120°) was found in 71.2% of eyes for CAant and in 88.8% for CApost. With increasing age, the occurrence of steep meridian aligned horizontally in CAant increased from 9.1% (age 20-29 years) to 31.8% (70-79 years), while vertical alignment decreased from 77.4% to 48.1%. Alignment of CApost mostly remained vertical (90.9%-80.7%). When CAant is vertical, CApost is vertical in 97% and CASim-K overestimates total corneal astigmatism (mean 0.11 ± 0.22 D). When CAant is horizontal, 18% of CApost is horizontal and CASim-K underestimates (mean 0.26 ± 0.31 D) total corneal astigmatism. The mean vector difference between CATCRP and CASim-K was 0.18 at 178° and exceeded 0.50 D in 9% of eyes. Total corneal astigmatism is overestimated by CASim-K in eyes with with-the-rule astigmatism and cannot be predicted safely in eyes that do not have with-the-rule astigmatism by anterior measurements only. Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc.
Fantes, F E; Waring, G O
The argon fluoride (193 nm) excimer laser is being used to change the anterior corneal curvature for correction of refractive errors. Uniformity of the surface following laser ablation may play an important role in the rate of epithelial healing and amount and type of stromal scarring. To test the effect of radiant exposure (fluence) on surface smoothness, we ablated rabbit corneas with the 193 nm argon fluoride excimer laser at nine radiant exposures from 50 to 850 mJ/cm2. A total energy of 100 J/cm2 was used for each ablation at a frequency of 1 Hz. Scanning electron microscopy demonstrated progressive improvement of surface smoothness with increasing radiant exposures. Transmission electron microscopy demonstrated no consistent increase in thickness to the surface condensate (pseudomembrane) with increasing radiant exposure. Improvement in surface quality associated with increasing radiant exposures may result from a more uniform depth of ablation per pulse in the corneal lamellae that absorb laser wavelengths differently. Radiant exposures at levels where the depth of ablation is the same regardless of increasing energy densities achieve a more uniform surface because inhomogeneities in the beam and variation in energy from pulse to pulse do not affect the ablation rate.
Evans, Margaret D M; Chaouk, Hassan; Wilkie, John S; Dalton, Beatrice A; Taylor, Sarah; Xie, Ruo Zhong; Hughes, Timothy C; Johnson, Graham; McFarland, Gail A; Griesser, Hans H; Steele, John G; Meijs, Gordon F; Sweeney, Deborah F; McLean, Keith M
Design principles for corneal implants are challenging and include permeability which inherently involves pore openings on the polymer surface. These topographical cues can be significant to a successful clinical outcome where a stratified epithelium is needed over the device surface, such as with a corneal onlay or corneal repair material. The impact of polymer surface topography on the growth and adhesion of corneal epithelial tissue was assessed using porous perfluoropolyether membranes with a range of surface topography. Surfaces were characterised by AFM and XPS, and the permeability and water content of membranes was measured. Biological testing of membranes involved a 21-day in vitro tissue assay to evaluate migration, stratification and adhesion of corneal epithelium. Similar parameters were monitored in vivo by surgically implanting membranes into feline corneas for up to 5 months. Data showed optimal growth and adhesion of epithelial tissue in vitro when polymer surface features were below a 150 nm RMS value. Normal processes of tissue growth and adhesion were disrupted when RMS values approached 300 nm. Data from the in vivo study confirmed these findings. Together, outcomes demonstrated the importance of surface topography in the design of implantable devices that depend on functional epithelial cover.
Shajari, Mehdi; Friderich, Stefan; Pour Sadeghian, Miad; Schmack, Ingo; Kohnen, Thomas
To evaluate and compare power and axis orientation of anterior and posterior astigmatism in eyes with keratoconus with healthy eyes. In this retrospective cohort study, we examined 861 eyes of 494 patients diagnosed with keratoconus at the Department of Ophthalmology, University Hospital Frankfurt, and 256 eyes of 256 healthy individuals. Using a Scheimpflug device (Pentacam HR), we measured the magnitude and axis orientation of anterior and posterior corneal astigmatism, corneal thickness, and conus location. The results were compared between different stages of the disease according to the Amsler-Krumeich classification and the control group. Magnitude of corneal astigmatism was 3.47 ± 2.10 diopters (D) on the anterior surface and 0.69 ± 0.40 D on the posterior surface in eyes across all keratoconus stages. We found a significant increase of anterior and posterior corneal astigmatism with progression of disease (P < 0.01, 1-way analysis of variance) and a significant correlation between anterior and posterior corneal astigmatism (r = 0.77, P < 0.01). In contrast to eyes of healthy individuals, in which posterior corneal axis alignment is vertical in most cases independent of anterior alignment, we found in eyes with keratoconus a match between anterior and posterior alignment when alignment was vertical in 97% of eyes, 46% when oblique and 61% when horizontal (Cohen kappa coefficient κ = 0.55, P < 0.01). With progression of disease, alignment of anterior and posterior corneal astigmatism became increasingly vertical. In eyes with keratoconus, posterior axis alignment of corneal astigmatism is in line with alignment of the anterior surface in the majority of cases. Posterior astigmatism axis alignment could potentially be used in algorithms to support diagnosis and staging of keratoconus.
Zhang, Wei; Chen, Jialin; Backman, Ludvig J; Malm, Adam D; Danielson, Patrik
The optimal functionality of the native corneal stroma is mainly dependent on the well-ordered arrangement of extracellular matrix (ECM) and the pressurized structure. In order to develop an in vitro corneal model, it is crucial to mimic the in vivo microenvironment of the cornea. In this study, the influence of surface topography and mechanical strain on keratocyte phenotype and ECM formation within a biomimetic 3D corneal model is studied. By modifying the surface topography of materials, it is found that patterned silk fibroin film with 600 grooves mm(-1) optimally supports cell alignment and ECM arrangement. Furthermore, treatment with 3% dome-shaped mechanical strain, which resembles the shape and mechanics of native cornea, significantly enhances the expression of keratocyte markers as compared to flat-shaped strain. Accordingly, a biomimetic 3D corneal model, in the form of a collagen-modified, silk fibroin-patterned construct subjected to 3% dome-shaped strain, is created. Compared to traditional 2D cultures, it supports a significantly higher expression of keratocyte and ECM markers, and in conclusion better maintains keratocyte phenotype, alignment, and fusiform cell shape. Therefore, the novel biomimetic 3D corneal model developed in this study serves as a useful in vitro 3D culture model to improve current 2D cultures for corneal studies.
Ramachandran, Charanya; Basu, Sayan; Sangwan, Virender S.
The cornea is a vital component of the eye because it provides approximately 70% of the refraction and focusing of incoming light. Being the outermost surface of the eye, it faces continuous stress from dryness, photodamage, infection, and injury; however, like the skin, the cornea regularly refreshes itself by shedding its epithelial cells, which are readily replaced, keeping the ocular surface stable and functional. This regular turnover of the corneal epithelial cells occurs through the stem cells in the limbus, an annular ring of a tissue surrounding the cornea, separating it from the sclera and the conjunctival membrane. The loss of this reserve of stem cells leads to a condition called limbal stem cell deficiency. Treatment for this disorder has evolved from transplanting whole limbal tissues to the affected eye to transplanting laboratory cultured limbal cells. This procedure is called cultivated limbal epithelial transplantation (CLET). Since its start in 1997, more than 1,000 CLET procedures have been reported from around the world, with varying degrees of success. In this paper, we compare the methods of cultivation and the outcomes and discuss some problem areas, use of other cells as substitutes for limbal epithelium, and various carrier materials used in transplantation. Our analysis suggests that CLET as a treatment for corneal surface damage has come of age. We also highlight a simpler procedure (simple limbal epithelial transplantation) that involves cultivation of limbal tissue in situ on the surface of the cornea in vivo and that has outcomes comparable to CLET. PMID:25205842
McCafferty, Sean J; Schwiegerling, Jim T; Enikov, Eniko T
We examined corneal surface response to an isolated thermal load. Cadaveric porcine eyes were pressurized and stabilized for processing and imaging. A carbon dioxide (CO2) laser (1.75 W) delivered a uniform disk of continuous wave thermal radiant energy to the exposed corneal stromal surface without ablation. Thermal load was determined by measuring corneal surface temperature during CO2 laser irradiation. Corneal profilometry was measured with broad-band optical interferometry before and after CO2 laser irradiation. Photomicrographs of the stromal surface were taken before and after irradiation, and the images were superimposed to examine changes in positional marks, examining mechanical alterations in the stromal surface. Thermal load from uniform laser irradiation without ablation produces central corneal steepening and paracentral flattening in the central 3-mm diameter. Q values, measuring asphericity in the central 2 mm of the cornea increased significantly and it was correlated with the temperature rise (R2=0.767). Surface roughness increased significantly and also was correlated with temperature rise (R2=0.851). The central stromal surface contracted and underwent characteristic morphologic changes with the applied thermal load, which correlated well with the temperature rise (R2=0.818). The thermal load created by CO2 laser irradiation creates a characteristic spectrum of morphologic changes on the porcine corneal stromal surface that correlates to the temperature rise and is not seen with inorganic, isotropic material. The surface changes demonstrated with the CO2 laser likely are indicative of temperature-induced transverse collagen fibril contraction and stress redistribution. Refractive procedures that produce significant thermal load should be cognizant of these morphologic changes.
Roth, H W
Use of a computer connected with a slit-lamp-video-camera detected changes in the cornea topography after wearing contact lenses on a daily basis. Also subtle surface changes were observed within the upper portion of the areas measured. These appeared to be spiral-shaped or cloudlike patterns as a result of wearing hard or soft contact lenses respectively. The changes observed appeared to have resulted from movement of the contact lens. However, this device has also been used to determine changes that are similar in early keratokonus. The computer can store data from 1600 sites on the surface; there sites are distributed over a 4-mm diameter area in the central cornea. On command the computer can display an image of the corneal surface. Images from hour 0 and 6 weeks later were compared to determine the topographic differences. The surface patterns observed after 6 weeks of wearing lenses appeared to be involve numerous small depressions.
Delgado, S; Velazco, J; Delgado Pelayo, R M; Ruiz-Quintero, N
To determine the correlation of higher order aberrations in anterior corneal surface and degree of keratoconus measured with a Scheimpflug camera. A descriptive, cross-sectional study was conducted on 152 eyes (both eyes of each patient) of patients with keratoconus, from January 2009 to April 2014. An examination was performed on the corneal aberrometry in the anterior corneal surface, and topographic mapping (by Amsler and Muckenhirn classification) was used to determine the degree of keratoconus. The correlation between high-order aberrations in anterior corneal surface and the degree of keratoconus was determined. Coma aberration significantly correlated with keratoconus severity (r=.60, P<.01), as well as with the high order aberration (r=.61, P<.01). Trefoil and keratoconus were weakly correlated (r=.34, P<.01). Higher order aberrations in anterior corneal surface were positively correlated with the degree of keratoconus in a similar way to the entire optical system. Copyright © 2016 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.
Dawson, Emma; Maino, Anna; Lee, John
Corneal tattoos have been previously used in managing corneal pathologies. We describe a case of a 28-year-old male who presented with intractable binocular diplopia, which was relieved with a corneal tattoo. This is a novel application of corneal tattooing for the alleviation of intractable binocular diplopia.
Zheng, Yan-Zhen; Chen, Yan-Peng; Qiu, Yan; Zhai, Guo-Guang; Li, Yao-Yu
AIM To describe the characteristics of modulation transfer function (MTF) of anterior corneal surface, and obtain the the normal reference range of MTF at different spatial frequencies and optical zones of the anterior corneal surface in myopes. METHODS Four hundred eyes from 200 patients were examined under SIRIUS corneal topography system. Phoenis analysis software was applied to simulate the MTF curves of anterior corneal surface at vertical and horizontal meridians at the 3, 4, 5, 6, 7mm optical zones of cornea. The MTF values at spatial frequencies of 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55 and 60 cycles/degree (c/d) were selected. RESULTS The MTF curve of anterior corneal surface decreased rapidly from low to intermediate frequency (0-15cpd) at various optical zones of cornea, the value decreased to 0 slowly at higher frequency (>15cpd). With the increase of the optical zones of cornea, MTF curve decreased gradually. 3) In the range of 3 mm- 6 mm optical zones of the cornea, the MTF values measured at horizontal meridian were greater than the corresponding values at horizontal meridian of each spatial frequency, the difference was statistically significant (P<0.05). At 7 mm optical zones of cornea, the MTF values measured at horizontal meridian were less than the corresponding values at vertical meridian at 10-60 spatial frequencies(cpd), and the difference was statistically significant in 25, 30, 35, 40, 45, 50 cpd (P<0.05). CONCLUSION MTF can be used to describe the imaging quality of optical systems at anterior corneal surface objectively in detail. PMID:22762049
Morphological changes of the peripheral nerves evaluated by high-resolution ultrasonography are associated with the severity of diabetic neuropathy, but not corneal nerve fiber pathology in patients with type 2 diabetes
Ishibashi, Fukashi; Taniguchi, Miki; Kojima, Rie; Kawasaki, Asami; Kosaka, Aiko; Uetake, Harumi
Aims/Introduction To evaluate the morphological changes of the median and posterior tibial nerve using high-resolution ultrasonography, and the corneal C fiber pathology by corneal confocal microscopy in type 2 diabetic patients. Materials and Methods The cross-sectional area, hypoechoic area and maximum thickness of the nerve fascicle of both nerves were measured by high-resolution ultrasonography in 200 type 2 diabetic patients, stratified by the severity of diabetic neuropathy, and in 40 age- and sex-matched controls. These parameters were associated with corneal C fiber pathology visualized by corneal confocal microscopy, neurophysiological tests and severity of diabetic neuropathy. Results The cross-sectional area, hypoechoic area and maximum thickness of the nerve fascicle of both nerves in patients without diabetic neuropathy were larger than those in control subjects (P < 0.05 to P < 0.001), and further increased relative to the severity of neuropathy (P < 0.0001). All morphological changes of both nerves were negatively associated with motor and sensory nerve conduction velocity (P = 0.01 to P < 0.0001), and directly associated with 2,000-Hz current perception threshold (P = 0.009 to P < 0.001). The significant corneal C fiber pathology occurred before developing the neuropathy, and deteriorated only in patients with the most severe neuropathy. The association between the morphological changes of both nerves and corneal C fiber pathology was poor. Conclusions The morphological changes in peripheral nerves of type 2 diabetic patients were found before the onset of neuropathy, and were closely correlated with the severity of diabetic neuropathy, but not with corneal C fiber pathology. PMID:25969719
Kling, Sabine; Hafezi, Farhad
In recent years, the interest in corneal biomechanics has strongly increased. The material properties of the cornea determine its shape and therefore play an important role in corneal ectasia and related pathologies. This review addresses the molecular origin of biomechanical properties, models for their description, methods for their characterisation, techniques for their modification, and computational simulation approaches. Recent research has focused on developing non-contact techniques to measure the biomechanical properties in vivo, on determining structural and molecular abnormalities in pathological corneas, on developing and optimising techniques to reinforce the corneal tissue and on the computational simulation of surgical interventions. A better understanding of corneal biomechanics will help to improve current refractive surgeries, allow an earlier diagnosis of ectatic disorders and a better quantification of treatments aiming at reinforcing the corneal tissue. © 2017 The Authors Ophthalmic & Physiological Optics © 2017 The College of Optometrists.
Wang, Yinhai; Williamson, Kate E; Kelly, Paul J; James, Jacqueline A; Hamilton, Peter W
Digital pathology provides a digital environment for the management and interpretation of pathological images and associated data. It is becoming increasing popular to use modern computer based tools and applications in pathological education, tissue based research and clinical diagnosis. Uptake of this new technology is stymied by its single user orientation and its prerequisite and cumbersome combination of mouse and keyboard for navigation and annotation. In this study we developed SurfaceSlide, a dedicated viewing platform which enables the navigation and annotation of gigapixel digitised pathological images using fingertip touch. SurfaceSlide was developed using the Microsoft Surface, a 30 inch multitouch tabletop computing platform. SurfaceSlide users can perform direct panning and zooming operations on digitised slide images. These images are downloaded onto the Microsoft Surface platform from a remote server on-demand. Users can also draw annotations and key in texts using an on-screen virtual keyboard. We also developed a smart caching protocol which caches the surrounding regions of a field of view in multi-resolutions thus providing a smooth and vivid user experience and reducing the delay for image downloading from the internet. We compared the usability of SurfaceSlide against Aperio ImageScope and PathXL online viewer. SurfaceSlide is intuitive, fast and easy to use. SurfaceSlide represents the most direct, effective and intimate human-digital slide interaction experience. It is expected that SurfaceSlide will significantly enhance digital pathology tools and applications in education and clinical practice.
Wang, Yinhai; Williamson, Kate E.; Kelly, Paul J.; James, Jacqueline A.; Hamilton, Peter W.
Background Digital pathology provides a digital environment for the management and interpretation of pathological images and associated data. It is becoming increasing popular to use modern computer based tools and applications in pathological education, tissue based research and clinical diagnosis. Uptake of this new technology is stymied by its single user orientation and its prerequisite and cumbersome combination of mouse and keyboard for navigation and annotation. Methodology In this study we developed SurfaceSlide, a dedicated viewing platform which enables the navigation and annotation of gigapixel digitised pathological images using fingertip touch. SurfaceSlide was developed using the Microsoft Surface, a 30 inch multitouch tabletop computing platform. SurfaceSlide users can perform direct panning and zooming operations on digitised slide images. These images are downloaded onto the Microsoft Surface platform from a remote server on-demand. Users can also draw annotations and key in texts using an on-screen virtual keyboard. We also developed a smart caching protocol which caches the surrounding regions of a field of view in multi-resolutions thus providing a smooth and vivid user experience and reducing the delay for image downloading from the internet. We compared the usability of SurfaceSlide against Aperio ImageScope and PathXL online viewer. Conclusion SurfaceSlide is intuitive, fast and easy to use. SurfaceSlide represents the most direct, effective and intimate human–digital slide interaction experience. It is expected that SurfaceSlide will significantly enhance digital pathology tools and applications in education and clinical practice. PMID:22292040
Dorfmueller, Simone; Tan, Hwee Ching; Ngoh, Zi Xian; Toh, Kai Yee; Peh, Gary; Ang, Heng-Pei; Seah, Xin-Yi; Chin, Angela; Choo, Andre; Mehta, Jodhbir S; Sun, William
Cell surface antigens are important targets for monoclonal antibodies, but they are often difficult to work with due to their association with the cell membrane. Phage display is a versatile technique that can be applied to generate binders against difficult targets. Here we used antibody phage display to isolate a binder for a rare and specialized cell, the human corneal endothelial cell. The human corneal endothelium is a medically important cell layer; defects in this layer account for about half of all corneal transplants. Despite its importance, no specific antigens have been found to mark this cell type. By panning a phage library directly on human corneal endothelial cells, we isolated an antibody that bound to these cells and not the other types of corneal cells. Subsequently, we identified the antibody's putative target to be CD166 by immunoprecipitation and mass spectrometry. This approach can be used to isolate antibodies against other poorly-characterized cell types, such as stem cells or cancer cells, without any prior knowledge of their discriminating markers.
To investigate whether the property of the surface of a fluid film to smooth irregularities in the underlying surface will cause the tear film to partially erase the effect of higher order corrections ablated onto a corneal surface during wavefront-guided refractive surgical correction. Coating flow theory shows that the film surface initially replicates the underlying surface. An iteration method is given to allow calculations to be made of the tear fluid flow and resulting surface change during the time between blinks. A new experimental technique is introduced using a corneal topographer and live video imaging to observe changes in tear surface curvature as the tear film flows. Tear flow changes in an eye with a high amount of aberration due to an unsuccessful LASIK procedure are simulated to show that while tear fluid occurs and causes changes in the tear/air surface, the change when expressed in terms of unwanted aberrations is below that which would cause any image degradation. Results of the live video technique on a cornea with an irregular surface 4 days after photorefractive keratectomy show that irregularities in the tear film surface immediately after a blink are not smoothed to any extent in the time before the next blink. Tear film flow following initial film formation by a blink can be demonstrated by computer simulation and observed with live corneal topography video. Tear film dynamics will not erase the effects of ablative corrections for higher order aberrations.
Ji, Yong Woo; Kim, Minseo; Kang, David Sung Yong; Reinstein, Dan Z; Archer, Timothy J; Choi, Jin Young; Kim, Eung Kweon; Lee, Hyung Keun; Seo, Kyoung Yul; Kim, Tae-Im
To determine the effect of lowering femtosecond laser energy on the surface quality of the intrastromal interface during small incision lenticule extraction (SMILE). Forty age- and diopter-matched female patients (40 eyes) with moderate myopia received SMILE with different energy levels (100 to 150 nJ) and fixed spot separation (4.5 μm). Five human corneal lenticules from each energy group were evaluated by atomic force microscopy and scanning electron microscopy (SEM). Both anterior and posterior surface characteristics of the lenticules were assessed. All measurements of surface roughness were approximately three times higher and in the anterior and posterior surface of the lenticules with the energy level of 150 nJ than with 100 nJ (P < .001). Furthermore, atomic force microscopy analysis found that energy differences of 15 nJ or more made a significant difference in surface roughness at energy levels of 115 nJ or higher. Interestingly, there was no significant difference in all roughness values of both surfaces among the 100, 105, and 110 nJ groups. In addition, all values of surface roughness were significantly positively correlated with laser energy for both anterior and posterior surfaces of the lenticule (P < .001). Consistent with atomic force microscopy results, SEM also showed that the SMILE lenticules in the higher laser energy group had more irregular surfaces. Lowering laser energy levels can improve surface quality of the lenticule of SMILE. To achieve better visual outcomes with faster recovery after the procedure, it is recommended to reduce the laser energy to less than 115 nJ at a spot separation of 4.5 μm. [J Refract Surg. 2017;33(9):617-624.]. Copyright 2017, SLACK Incorporated.
DeLoss, Karen S; Fatteh, Nadeem H; Hood, Christopher T
To compare the ocular characteristics and visual outcomes of eyes with corneal ectasia that were fitted with the Prosthetic Replacement of the Ocular Surface Ecosystem (PROSE) scleral device to those that underwent keratoplasty. Retrospective, comparative case series. We reviewed the charts of consecutive patients with corneal ectasia that were evaluated for PROSE or underwent keratoplasty at our institution. Clinical data, topographic indices, and corneal thickness were reviewed, and eyes were stratified according to the Amsler-Krumeich classification for severity of ectasia. Only the more severe eye of each patient was included in the study. We compared visual acuity before and after PROSE fitting or keratoplasty. For PROSE evaluations, achievement of satisfactory fit and continued wear at 1 year of follow-up were recorded. From 2010 to 2012, 36 patients underwent PROSE evaluation for corneal ectasia while 37 patients underwent keratoplasty for the same indication. All eyes were successfully fitted with the PROSE device. Eyes in the keratoplasty group had more severe ectasia than eyes in the PROSE group (P = .038). Visual acuity was achieved more rapidly in the PROSE cohort compared to keratoplasty, and mean visual acuity was significantly better for all eyes (P < .0001) and when including only eyes with stage 4 ectasia (P < .001). More eyes with stage 4 ectasia achieved 20/25 visual acuity after PROSE than after keratoplasty (P = .003). At 1 year follow-up in the PROSE cohort, Snellen acuity was 20/28 (P = .108 vs keratoplasty), improving to 20/25 with over-refraction (P = .006 vs keratoplasty). Eyes with advanced corneal ectasia can be successfully fitted with the PROSE device, and the visual acuity outcome for stage 4 ectasia was better and more rapid compared to keratoplasty. The acuity remained excellent with 1 year of follow-up. PROSE evaluation should be considered in patients with advanced corneal ectasia before proceeding to keratoplasty, especially if
Dawson, Charlotte; Sanchez, Rick F
To identify the prevalence of corneal ulceration in dogs receiving prophylactic gel lubrication under general anesthesia (GA). An ophthalmic examination was performed before premedication and 24 h after GA in 100 dogs (199 eyes) undergoing nonophthalmic procedures. Individuals with known pre-existing ocular surface conditions were excluded. An ocular lubricating gel containing carmellose sodium was applied by the anesthetist at induction and every 2-4 h until extubation. Logistic regression analysis was used to calculate risk factors for ulcerative disease, including signalment, length of GA, patient position, procedure performed, pre-, and post-GA ophthalmic examination findings and admitting service. A Wilcoxon rank sum test compared pre- and post-GA Schirmer tear test-1 (STT-1) values. One dog (0.5% of total eyes) developed fluorescein stain uptake consistent with superficial corneal ulceration that resolved within 48 h with supportive treatment. Twenty-five (18.6% of total eyes) developed a faint, patchy corneal uptake of stain in the axial cornea that was consistent with epithelial erosion. All erosions resolved with lubrication 24 h later. The decrease in STT-1 readings at 24 h post-GA was statistically significant from those pre-GA (P < 0.001). No significant risk factors for corneal erosion/ulceration were identified. The results of this study show that a basic protocol of prophylactic lubrication during GA was associated with a low prevalence of corneal ulceration but a higher prevalence of epithelial erosion. In addition, the study supports the need for post-GA corneal examination. © 2015 American College of Veterinary Ophthalmologists.
... Injuries Dystrophies - conditions in which parts of the cornea lose clarity due to a buildup of cloudy material Treatments of corneal disorders include medicines, corneal transplantation, and corneal laser surgery. NIH: National Eye Institute
Douthwaite, W A
AIMS/BACKGROUND--This study was carried out to assess the accuracy of the EyeSys videokeratoscope by using convex ellipsoidal surfaces of known form. METHODS--PMMA convex ellipsoidal buttons were calibrated using Form Talysurf analysis which allowed subsequent calculation of the vertex radius and p value of the surface. The EyeSys videokeratoscope was used to examine the same ellipsoids. The tabular data provided by the instrument software were used to plot a graph of r2 versus y2 where r is the measured radius at y, the distance from the corneal point being measured to the surface vertex. The intercept on the ordinate of this graph gives the vertex radius and the slope the p value. The results arising from the Talysurf and the EyeSys techniques were compared. RESULTS--The EyeSys videokeratoscope gave readings for both vertex radius and p value that were higher than those of the Talysurf analysis. The vertex radius was around 0.1 mm greater. The p value results were similar by the two methods for p values around unity but the EyeSys results were higher and the discrepancy increased as the p value approached that of a paraboloid. CONCLUSIONS--Although the videokeratoscope may be useful in comparative studies of the cornea, there must be some doubt about the absolute values displayed. The disagreement is sufficiently large to suggest that the instrument may not be accurate enough for contact lens fitting purposes. PMID:7488595
von Spiessen, Lena; Karck, Julia; Rohn, Karl; Meyer-Lindenberg, Andrea
To compare the TonoVet(®) rebound tonometer with the Tono-Pen Vet(®) applanation tonometer in a larger number of glaucomatous eyes and to evaluate the effect of different corneal pathologies on both tonometers. In 26 eyes with clinical signs of glaucoma, intraocular pressure (IOP) was measured using the TonoVet(®) followed by the Tono-Pen Vet(®) . In 29 eyes with focal corneal pathology (e.g., corneal scarring, edema, pigmentation), both tonometers were used successively to measure IOP in one unaffected area of the cornea, as well as on the lesion itself. Impact on measurement results was assessed comparing the deviation in IOP readings of each tonometer between the two localizations. Statistical data analysis included paired t-tests and regression analysis using sas software (version 9.2; SAS Institute, Cary, NC). In glaucomatous eyes, the TonoVet(®) consistently yielded higher values of IOP than the Tono-Pen Vet(®) as can be quantified by the regression equation IOP (TonoVet(®) ) [mmHg] = 1.12 * IOP (Tono-Pen Vet(®) ) [mmHg] + 11.5 with R(2) = 0.91 and P < 0.0001. Depending on the type and degree of corneal pathology, the deviation in IOP resulting from measurements on altered cornea ranged from -6 to 16 mmHg for the TonoVet(®) and -7 to 20 mmHg for the Tono-Pen Vet(®) , respectively. On average, the effect of corneal disease on IOP measurements was lower for the TonoVet(®) by 1.14 mmHg. Rebound tonometry appears to be a valuable alternative to established applanation tonometry in patients with ocular disease such as glaucoma and corneal disorders. In patients suffering from glaucoma, the same type of tonometer should be used for follow-up examinations, as measurement results of the TonoVet(®) and the Tono-Pen Vet(®) differ substantially with increasing IOP. Corneal pathology has considerable influence on both tonometers with the degree of over- or underestimation of IOP depending on the alteration of biomechanical properties of the cornea inflicted
Saban, Daniel R
Dendritic cells (DCs) are highly potent stimulators of the immune system, and their contribution as such to the pathogenesis of corneal and ocular surface inflammatory disease has been well established. These vigorous antigen-presenting cells are reliant upon their effective migration from peripheral tissues (e.g., those of the ocular surface) to the lymphoid organs, where immune responses are triggered and can then cause disease. The chemokine receptor CCR7 expressed on DCs has emerged as the master mediator of this highly complex migratory process, and thus it is important in causing corneal and ocular surface inflammation. Furthermore, CCR7 has received considerable attention as a potential therapeutic target, as topically instilled antagonists of this receptor are quite effective therapeutically in a mouse model of ocular allergy. These findings and more are reviewed in the current article. In addition, the understanding regarding CCR7 function in mice and humans, and the biology of DCs that populate the ocular surface are also detailed herein. The involvement of DCs and their expression of CCR7 in corneal and ocular surface diseases such as in ocular allergy, dry eye disease, immune rejection and more, are also reviewed here.
Liu, Yang; Lv, Huilin; Ren, Li; Xue, Guanhua; Wang, Yingjun
Cornea disease is the second cause of blindness and keratoplasty is the most commonly performed option for visual rehabilitation of patients with corneal blindness. However, the clinical treatment has been drastically limited due to a severe shortage of high-quality donor corneas. Although collagen film with outstanding biocompatibility has promising application in corneal tissue engineering, the moisturizing properties of collagen-based materials must be further improved to satisfy the requirements of clinical applications. This paper describes a novel collagen-based film with high moisture capacity reinforced by surface grafting of chondroitin sulfate. The collagen-chondroitin sulfate (abbreviated as Col-CS) film was analyzed by Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy and its hydrophilic property, moisture retention, optical property, and mechanical performance had been tested. The moisture-retaining capacity is found to be improved with the introduction of chondroitin sulfate, and the Col-CS membrane performs better mechanical properties than the collagen film. Moreover, the modified film proves excellent biocompatibility for the proliferation of human corneal epithelial cells in vitro. This Col-CS film with good moisturizing properties can reduce the risk of xerophthalmia and is expected to increase the implant success rate in clinic patients with corneal defects.
Doss, James D.; Hutson, Richard L.
The disclosure relates to a circulating saline electrode for changing corneal shape in eyes. The electrode comprises a tubular nonconductive electrode housing having an annular expanded base which has a surface substantially matched to a subject corneal surface. A tubular conductive electrode connected to a radiofrequency generating source is disposed within the electrode housing and longitudinally aligned therewith. The electrode has a generally hemispherical head having at least one orifice. Saline solution is circulated through the apparatus and over the cornea to cool the corneal surface while radiofrequency electric current emitted from the electrode flows therefrom through the cornea to a second electrode, on the rear of the head. This current heats the deep corneal stroma and thereby effects corneal reshaping as a biological response to the heat.
Nakamura, Takahiro; Hamuro, Junji; Takaishi, Mikiro; Simmons, Szandor; Maruyama, Kazuichi; Zaffalon, Andrea; Bentley, Adam J.; Kawasaki, Satoshi; Nagata-Takaoka, Maho; Fullwood, Nigel J.; Itami, Satoshi; Sano, Shigetoshi; Ishii, Masaru; Barrandon, Yann; Kinoshita, Shigeru
Corneal integrity and transparency are indispensable for good vision. Cornea homeostasis is entirely dependent upon corneal stem cells, which are required for complex wound-healing processes that restore corneal integrity following epithelial damage. Here, we found that leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) is highly expressed in the human holoclone-type corneal epithelial stem cell population and sporadically expressed in the basal cells of ocular-surface epithelium. In murine models, LRIG1 regulated corneal epithelial cell fate during wound repair. Deletion of Lrig1 resulted in impaired stem cell recruitment following injury and promoted a cell-fate switch from transparent epithelium to keratinized skin-like epidermis, which led to corneal blindness. In addition, we determined that LRIG1 is a negative regulator of the STAT3-dependent inflammatory pathway. Inhibition of STAT3 in corneas of Lrig1–/– mice rescued pathological phenotypes and prevented corneal opacity. Additionally, transgenic mice that expressed a constitutively active form of STAT3 in the corneal epithelium had abnormal features, including corneal plaques and neovascularization similar to that found in Lrig1–/– mice. Bone marrow chimera experiments indicated that LRIG1 also coordinates the function of bone marrow–derived inflammatory cells. Together, our data indicate that LRIG1 orchestrates corneal-tissue transparency and cell fate during repair, and identify LRIG1 as a key regulator of tissue homeostasis. PMID:24316976
Sidiropoulos, A. A.; Lakakis, K. N.; Mouza, V. K.
The technology of 3D laser scanning is considered as one of the most common methods for heritage documentation. The point clouds that are being produced provide information of high detail, both geometric and thematic. There are various studies that examine techniques of the best exploitation of this information. In this study, an algorithm of pathology localization, such as cracks and fissures, on complex building surfaces is being tested. The algorithm makes use of the points' position in the point cloud and tries to distinguish them in two groups-patterns; pathology and non-pathology. The extraction of the geometric information that is being used for recognizing the pattern of the points is being accomplished via Principal Component Analysis (PCA) in user-specified neighborhoods in the whole point cloud. The implementation of PCA leads to the definition of the normal vector at each point of the cloud. Two tests that operate separately examine both local and global geometric criteria among the points and conclude which of them should be categorized as pathology. The proposed algorithm was tested on parts of the Gazi Evrenos Baths masonry, which are located at the city of Giannitsa at Northern Greece.
Carvalho, Luis A.
Zernike Polynomials have been successfully used for many years in optics. Nevertheless there are some recent discussions regarding their accuracy when applied to surfaces such as the human cornea. A set of synthetic surfaces resembling several common corneal anomalies was sampled and was also used to compute the optical path difference using a simple ray-tracing procedure. The Root Mean Square Error between the Zernike Polynomials fit and the theoretical elevation and WF error surface was computed for both surfaces and for all number of Zernike terms. We have found that RMSE for the simplest, most symmetric corneal surface (spherical shape) and for the most complex shape (post-radial keratotomy) both the optical path difference and surface elevation, for 1 through 36 Zernike terms, range from: 421.4 to 0.8 microns, and 421.4 to 8.2 microns, respectively; mean RMSE for maximum Zernike terms for both surfaces were 4.5 microns. Computations in this work suggest that, for surfaces such as post-RK, keratoconus or post-keratoplasty, even more than 36 terms may be necessary in order to obtain minimum precision requirements. We suggest that the number of Zernike Polynomial should not be a global fixed conventional value but rather based on specific surface properties.
Avadhanam, Venkata S; Smith, Helen E; Liu, Christopher
According to the World Health Organization, globally 4.9 million are blind due to corneal pathology. Corneal transplantation is successful and curative of the blindness for a majority of these cases. However, it is less successful in a number of diseases that produce corneal neovascularization, dry ocular surface and recurrent inflammation, or infections. A keratoprosthesis or KPro is the only alternative to restore vision when corneal graft is a doomed failure. Although a number of KPros have been proposed, only two devices, Boston type-1 KPro and osteo-odonto-KPro, have came to the fore. The former is totally synthetic and the latter is semi-biological in constitution. These two KPros have different surgical techniques and indications. Keratoprosthetic surgery is complex and should only be undertaken in specialized centers, where expertise, multidisciplinary teams, and resources are available. In this article, we briefly discuss some of the prominent historical KPros and contemporary devices. PMID:25945031
Dou, Rui; Wang, Yan; Xu, Lulu; Wu, Di; Wu, Wenjing; Li, Xiaojing
To investigate and compare corneal biomechanical changes in the form of corneal hysteresis (CH) and corneal resistance factor (CRF) after small-incision lenticule extraction (SMILE) and laser-assisted subepithelial keratectomy (LASEK). In this retrospective observational study, patients who underwent either SMILE (36 eyes, 21 patients) or LASEK (35 eyes, 19 patients) were included. Data were collected preoperatively and at 1 and 3 months postoperatively, which included corneal topography and Ocular Response Analyzer values of CH, CRF, and intraocular pressure (IOP). Differences between both surgical groups and the relationships between variables were evaluated. CH, CRF, Goldmann IOP, and corneal compensated IOP after surgery were significantly lower than the preoperative values (P < 0.05) in both surgical groups. Lenticule thickness (LT) correlated with ΔCRF (Δ = postoperative - preoperative value) in the SMILE group (r = -0.513, P = 0.001), but the ablation depth (AD) and ΔCRF showed no correlation in the LASEK group (r = -0.297, P = 0.083). In the SMILE group, ΔCRF/LT (-0.036 ± 0.01) and ΔCH/LT (-0.021 ± 0.01) values were significantly lower than ΔCRF/AD (-0.048 ± 0.02) and ΔCH/AD (-0.026 ± 0.02) values in the LASEK group (P < 0.05). Both SMILE and LASEK alter corneal biomechanical strength. However, the changes induced by SMILE are more predictable than those induced by LASEK. In terms of per unit tissue removed, SMILE seems to have less effect on corneal biomechanics than LASEK, which may be due to preservation of the stiffer anterior stroma.
Lim, Pauline; Ridges, Ryan; Jacobs, Deborah S; Rosenthal, Perry
To report experience in the treatment of persistent corneal epithelial defect using overnight wear of a prosthetic device for the ocular surface. Retrospective interventional case series. A clinical database of patients who underwent prosthetic replacement of the ocular surface ecosystem (PROSE) treatment from March 2003 to August 2008 was searched to identify patients treated for persistent corneal epithelial defect. In early 2003, overnight wear of a PROSE device and addition of commercially available, nonpreserved, topical ophthalmic moxifloxacin to the saline in the device reservoir became standard practice at this center when treating persistent corneal epithelial defect. Medical records were abstracted to obtain underlying diagnoses, previous treatments, days to re-epithelialization, and complications for subsequent analysis. PROSE treatment incorporating overnight wear, with adjunctive use of moxifloxacin, was employed in 20 eyes of 19 patients for a total of 372 days. Re-epithelialization occurred in 17 of 20 eyes. Median duration of treatment incorporating overnight wear was 8.5 days (range = 2-76 days). Healing occurred in ≤7 days in 12 eyes, 8-14 days in 3 eyes, and >14 days in 2 eyes (range = 1-35 days). There were no cases of microbial keratitis. Overnight wear of a PROSE device is effective in promoting healing of persistent corneal epithelial defect. In comparison to an earlier series from this center, the rate of microbial keratitis as a complication of treatment has been reduced with the use of a nonpreserved topical fourth-generation fluoroquinolone in the device reservoir. Copyright © 2013 Elsevier Inc. All rights reserved.
Diurnal Variation of Tight Junction Integrity Associates Inversely with Matrix Metalloproteinase Expression in Xenopus laevis Corneal Epithelium: Implications for Circadian Regulation of Homeostatic Surface Cell Desquamation
Wiechmann, Allan F.; Ceresa, Brian P.; Howard, Eric W.
Background and Objectives The corneal epithelium provides a protective barrier against pathogen entrance and abrasive forces, largely due to the intercellular junctional complexes between neighboring cells. After a prescribed duration at the corneal surface, tight junctions between squamous surface cells must be disrupted to enable them to desquamate as a component of the tissue homeostatic renewal. We hypothesize that matrix metalloproteinase (MMPs) are secreted by corneal epithelial cells and cleave intercellular junctional proteins extracellularly at the epithelial surface. The purpose of this study was to examine the expression of specific MMPs and tight junction proteins during both the light and dark phases of the circadian cycle, and to assess their temporal and spatial relationships in the Xenopus laevis corneal epithelium. Methodology/Principal Findings Expression of MMP-2, tissue inhibitor of MMP-2 (TIMP-2), membrane type 1-MMP (MT1-MMP) and the tight junction proteins occludin and claudin-4 were examined by confocal double-label immunohistochemistry on corneas obtained from Xenopus frogs at different circadian times. Occludin and claudin-4 expression was generally uniformly intact on the surface corneal epithelial cell lateral membranes during the daytime, but was frequently disrupted in small clusters of cells at night. Concomitantly, MMP-2 expression was often elevated in a mosaic pattern at nighttime and associated with clusters of desquamating surface cells. The MMP-2 binding partners, TIMP-2 and MT1-MMP were also localized to surface corneal epithelial cells during both the light and dark phases, with TIMP-2 tending to be elevated during the daytime. Conclusions/Significance MMP-2 protein expression is elevated in a mosaic pattern in surface corneal epithelial cells during the nighttime in Xenopus laevis, and may play a role in homeostatic surface cell desquamation by disrupting intercellular junctional proteins. The sequence of MMP secretion and
Samoilă, O; Totu, Lăcrămioara; Călugăru, M
A variety of corneal pathology can lead to corneal ulcers and perforations. A deep corneal ulcer may need surgical treatment to allow good volume restoration and reepithelisation. Corneal perforation must be sealed and when the perforation is large, the task of repairing the defect can be underwhelming. The elegant solution is the corneal transplant, but this is not always readily available, especially in undeveloped countries. We present here two cases with different solutions to seal the perforated cornea: the first one has a large peripheral defect and it is successfully sealed with scleral patch and the second one is central with small perforation and is successfully sealed with multilayered amniotic membrane. Both cases are followed for over 12 months and demonstrate good corneal restoration (both on clinical examination and corneal topography). Sclera and amniotic membrane can be used to seal corneal defects when corneal transplant is not readily available.
Yu, Qing; Wu, Jiang-Xiu; Zhang, He-Ning; Ye, Sheng; Dong, Shi-Qi; Zhang, Chen-Hao
AIM To record aberrations with a corneal topographic device on the anterior surface of the cornea at different time-points prior to wearing and following discontinued use of rigid gas permeable (RGP) contact lenses. The effect of wearing RGP on the anterior surface of the cornea was discussed to provide guidance for clinical refractive error correction. METHODS The study objects were 24 eyes from 24 patients. All patients underwent identical examination procedures prior to lens use, as well as afterwards, including slit-lamp examination, non-contact tonometer measurement, computer optometry and corneal curvature measurement, subjective refraction test, and corneal topography analysis. The patients wore contact lenses everyday for 1 month and then discontinued. Corneal topographies were recorded at certain time points of 30 minutes, 1 day, 3, 7 and 14 days following use. RESULTS Total corneal aberration at each time point following discontinued use of RGP contact lenses was less than the time point prior to use. Detailed results were as follows: root mean square (RMS) (pre)=(1.438±0.328)µm, RMS (30 minutes)=(1.076±0.355)µm, RMS (1 day)=(1.362±0.402)µm, RMS (3 days)=(1.373±0.398)µm, RMS (7 days)=(1.387±0.415)µm, and RMS (14 days)=(1.430±0.423)µm. Results showed that at 30 minutes after discontinued use of RGP contact lenses, almost all 2nd- and 3rd-order aberrations change. Quadrafoil Z10 and spherical Z12 of the 4th-order were also changed. Alterations to Z5, Z6, and Z12 at 1 day after discontinued use were significant differences compared with the time period prior to RGP use: Z5 and Z6 decreased, and Z12 increased slightly. Z5 and Z6 remained decreased at 3 days after discontinued use, but Z9 and Z10 continued to increase and Z12 returned to levels prior to RGP use. At 14 days after discontinued use, all aberrations were not significantly different from the values prior to use. CONCLUSION The use RGP contact lenses greatly reduced total aberration of
Ferrari, Giulio; Bignami, Fabio; Giacomini, Chiara; Capitolo, Eleonora; Comi, Giancarlo; Chaabane, Linda; Rama, Paolo
To test whether a corneal injury can stimulate inflammation in the trigeminal ganglion (TG), a structure located in the brain. At 4 and 8 days after alkali burn induced in the right eyes of mice, in vivo magnetic resonance imaging (MRI) of the brain was done before and after ultrasmall superparamagnetic iron oxide nanoparticle (USPIO) contrast to track macrophages. Trigeminal ganglia were stained for Prussian Blue and inflammatory cell markers. Interleukin-1β, TNF-α, and VEGF-A transcripts were quantified on days 1, 4, and 8, and 4 days after corneal topical anti-inflammatory treatment with 0.2% dexamethasone. The expression of Substance P and its receptor NK-1R was also measured in the TG on day 4. Corneal alkali burn induced leukocyte infiltration, including T cells, in the right TG at 4 and 8 days. In vivo MRI showed an increased contrast uptake in the right TG, which peaked at day 8. Prussian Blue(+) USPIO(+) macrophages were observed in the right TG and exhibited an M2 phenotype. The M2-macrophage infiltration was preponderant in the TG after damage. The proinflammatory cytokines Substance P and NK-1R were significantly increased in both the TGs. The expression of IL-1β and VEGF-A was significantly reduced in the right TG with dexamethasone treatment. We suggest, for the first time, inflammatory involvement of brain structures following ocular surface damage. Our findings support the hypothesis that the neuropeptide Substance P may be involved in the propagation of inflammation from the cornea to the TG through corneal nerves. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.
Bueeler, M.; Donitzky, Ch.; Mrochen, M.
The effectiveness of the corneal ablation process in refractive surgery is mostly evaluated by indirect measures of vision or optical quality such as post-operative refraction or wavefront aberrometry. Yet, the effective amount of corneal tissue removed in the treatment can only be determined by correctly overlapping a pre- and a post-operative topography measurement. However such an overlap is not trivial due to the discrepancy in the centration axes used in the measurement and the treatment, as well as due to the shift of ocular axes through the treatment or tilt between the two surfaces. We therefore present two methods for overlapping pre- and post-operative topographies for the purpose of extracting an effective corneal ablation profile. Method one uses a 3-dimensional profile matching algorithm and cross-correlation analysis on surface rings outside the optical zone of the topographies. Method two employs a surface normal matching routine to align the two surfaces along their common ablation axis. The profile matching method implies the problem that it requires measurement data outside of the optical zone which was found to be uncertain with placido-disk-based topographers. Method number two is more simple and implies the advantage of using measurement data within the optical zone. For regular profiles the extracted ablation profiles showed a very good match with the planned ones. Surprisingly, even for highly irregular profiles of topography-guided laser treatments the method delivered reasonable overlaps when being compared to the planned profiles. Analysis of the effective tissue removal yields valuable information on the quality of the ablation process.
Klintworth, Gordon K
The term corneal dystrophy embraces a heterogenous group of bilateral genetically determined non-inflammatory corneal diseases that are restricted to the cornea. The designation is imprecise but remains in vogue because of its clinical value. Clinically, the corneal dystrophies can be divided into three groups based on the sole or predominant anatomical location of the abnormalities. Some affect primarily the corneal epithelium and its basement membrane or Bowman layer and the superficial corneal stroma (anterior corneal dystrophies), the corneal stroma (stromal corneal dystrophies), or Descemet membrane and the corneal endothelium (posterior corneal dystrophies). Most corneal dystrophies have no systemic manifestations and present with variable shaped corneal opacities in a clear or cloudy cornea and they affect visual acuity to different degrees. Corneal dystrophies may have a simple autosomal dominant, autosomal recessive or X-linked recessive Mendelian mode of inheritance. Different corneal dystrophies are caused by mutations in the CHST6, KRT3, KRT12, PIP5K3, SLC4A11, TACSTD2, TGFBI, and UBIAD1 genes. Knowledge about the responsible genetic mutations responsible for these disorders has led to a better understanding of their basic defect and to molecular tests for their precise diagnosis. Genes for other corneal dystrophies have been mapped to specific chromosomal loci, but have not yet been identified. As clinical manifestations widely vary with the different entities, corneal dystrophies should be suspected when corneal transparency is lost or corneal opacities occur spontaneously, particularly in both corneas, and especially in the presence of a positive family history or in the offspring of consanguineous parents. Main differential diagnoses include various causes of monoclonal gammopathy, lecithin-cholesterol-acyltransferase deficiency, Fabry disease, cystinosis, tyrosine transaminase deficiency, systemic lysosomal storage diseases (mucopolysaccharidoses
Rubin, E.; Farber, J.L. )
This book contains 29 chapters. Some of the titles are: Genetic and Systemic Diseases; Cell Injury; Inflammation; The Gastrointestinal o Tract; The Pancreas; Environmental and Nutritional Pathology; Infectious and Parasitic Diseases; and Blood Vessels.
Kaste, Sue C; Fuller, Christine E; Saharia, Ashish; Neel, Michael D; Rao, Bhaskar N; Daw, Najat C
Osteosarcoma (OS) arising from the surface of bone is far less common than its intramedullary counterpart. Although surface OSs share some radiographic and clinical features, they can be divided into three distinct histologic subtypes. We reviewed the clinical, radiographic, and pathologic features of 14 cases of pediatric surface OS treated at St. Jude Children's Research Hospital between 1970 and 2003. Seven patients had parosteal, five had periosteal, and two had high-grade surface OS. The median age at diagnosis was 16.2 years (range, 13.6-18.5 years). Nine patients were male; 11 were Caucasian. None had metastatic disease at diagnosis. Primary tumor sites included distal femur (n = 6), mid to proximal femur (n = 4), and mid to proximal tibia (n = 4). All 14 patients were treated with surgery, and 7 (1 with parosteal, 4 with periosteal, 2 with high-grade tumors) received chemotherapy. One patient experienced pulmonary metastasis of periosteal OS 16 months and 43 months after diagnosis; long-term disease-free survival followed resection of the metastatic tumors. Twelve patients remained alive and disease-free a median of 10 years (range, 1.5-25.4 years) after diagnosis. One patient died of high-grade surface OS 1.8 years after diagnosis, and one patient with periosteal OS died of gastric cancer 18.2 years after diagnosis of OS. The histologic grade predicts the clinical behavior of pediatric surface OS. Complete resection is the treatment of choice regardless of tumor subtype. Whereas chemotherapy is not indicated for parosteal OS, its role in periosteal OS remains controversial.
Gonzalez-Andrades, Miguel; Cardona, Juan de la Cruz; Ionescu, Ana Maria; Mosse, Charles A; Brown, Robert A
Tissues and biomaterials used for corneal surface repair require fulfilling specific optical standards prior to implantation in the patient. However, there is not a feasible evaluation method to be applied in clinical or Good Manufacturing Practice settings. In this study, we describe and assess an innovative easy-applied photographic-based method (PBM) for measuring functional optical blurring and transparency in corneal surface grafts. Plastic compressed collagen scaffolds (PCCS) and multilayered amniotic membranes (AM) samples were optically and histologically evaluated. Transparency and image blurring measures were obtained by PBM, analyzing photographic images of a standardized band pattern taken through the samples. These measures were compared and correlated to those obtained applying the Inverse Adding-Doubling (IAD) technique, which is the gold standard method. All the samples used for optical evaluation by PBM or IAD were histological suitable. PCCS samples presented transmittance values higher than 60%, values that increased with increasing wavelength as determined by IAD. The PBM indicated that PCCS had a transparency ratio (TR) value of 80.3 ± 2.8%, with a blurring index (BI) of 50.6 ± 4.2%. TR and BI obtained from the PBM showed a high correlation (ρ>|0.6|) with the diffuse transmittance and the diffuse reflectance, both determined using the IAD (p<0.005). The AM optical properties showed that there was a largely linear relationship between the blurring and the number of amnion layers, with more layers producing greater blurring. This innovative proposed method represents an easy-applied technique for evaluating transparency and blurriness of tissues and biomaterials used for corneal surface repair.
Gonzalez-Andrades, Miguel; Cardona, Juan de la Cruz; Ionescu, Ana Maria; Mosse, Charles A.; Brown, Robert A.
Purpose Tissues and biomaterials used for corneal surface repair require fulfilling specific optical standards prior to implantation in the patient. However, there is not a feasible evaluation method to be applied in clinical or Good Manufacturing Practice settings. In this study, we describe and assess an innovative easy-applied photographic-based method (PBM) for measuring functional optical blurring and transparency in corneal surface grafts. Methods Plastic compressed collagen scaffolds (PCCS) and multilayered amniotic membranes (AM) samples were optically and histologically evaluated. Transparency and image blurring measures were obtained by PBM, analyzing photographic images of a standardized band pattern taken through the samples. These measures were compared and correlated to those obtained applying the Inverse Adding-Doubling (IAD) technique, which is the gold standard method. Results All the samples used for optical evaluation by PBM or IAD were histological suitable. PCCS samples presented transmittance values higher than 60%, values that increased with increasing wavelength as determined by IAD. The PBM indicated that PCCS had a transparency ratio (TR) value of 80.3±2.8%, with a blurring index (BI) of 50.6±4.2%. TR and BI obtained from the PBM showed a high correlation (ρ>|0.6|) with the diffuse transmittance and the diffuse reflectance, both determined using the IAD (p<0.005). The AM optical properties showed that there was a largely linear relationship between the blurring and the number of amnion layers, with more layers producing greater blurring. Conclusions This innovative proposed method represents an easy-applied technique for evaluating transparency and blurriness of tissues and biomaterials used for corneal surface repair. PMID:26566050
Jun, Bokkwan; Berdahl, John P; Kim, Terry
To evaluate the change and difference in the corneal surface, incision, and handpiece temperatures during longitudinal and torsional ultrasound (US) phacoemulsification with standard incisions (2.75 mm) and microincisions (2.20 mm) and the thermal effect on wounds. Department of Ophthalmology, Duke University, Durham, North Carolina, USA. In this prospective study, human cadaver eyes had simulated phacoemulsification. Group 1 had a 2.75 mm incision with 100% longitudinal US; Group 2, a 2.20 mm incision with 100% longitudinal US; Group 3, a 2.75 mm incision with 100% torsional US; and Group 4, a 2.20 mm incision with 100% torsional US. During phacoemulsification, the corneal incision was evaluated by surgical microscopy and scanning electron microscopy (SEM) and images of the corneal surface, incision, and handpiece were captured with an infrared camera. Twelve eyes (3 each group) were evaluated. The maximum incision temperature was higher in the longitudinal groups than in the torsional groups. With the same US modality, the maximum microincision temperature was higher than the maximum standard incision temperature. After application of full power for 40 seconds, wound burn was observed in all eyes in the longitudinal groups and no eyes in the torsional groups. On SEM, there was more extensive loss of Descemet membrane in the longitudinal groups than in the torsional groups. Incision temperature was influenced by US modality and was significantly lower with torsional US than with longitudinal US. Using torsional US with smaller incisions may decrease the risk for wound burn in eyes with denser cataracts. (c) 2010 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.
Jolly, Amber L; Agarwal, Paresh; Metruccio, Matteo M E; Spiciarich, David R; Evans, David J; Bertozzi, Carolyn R; Fleiszig, Suzanne M J
Cell surface glycosylation is thought to be involved in barrier function against microbes at mucosal surfaces. Previously we showed that the epithelium of healthy mouse corneas becomes vulnerable to P. aeruginosa adhesion if it lacks the innate defense protein MyD88 (myeloid differentiation primary response gene 88), or after superficial injury by blotting with tissue paper. Here we explored their effect on corneal surface glycosylation using a metabolic label, tetra-acetylated N-azidoacetylgalactosamine (Ac4GalNAz). Ac4GalNAz treatment labeled the surface of healthy mouse corneas, leaving most cells viable, and bacteria preferentially associated with GalNAz-labeled regions. Surprisingly, corneas from MyD88(-/-) mice displayed similar GalNAz labeling to wild-type corneas, but labeling was reduced and patchy on IL-1 receptor (IL-1R)-knockout mouse corneas (P < 0.05, ANOVA). Tissue paper blotting removed GalNAz-labeled surface cells, causing DAPI labeling (permeabilization) of underlying cells. MS of material collected on the tissue paper blots revealed 67 GalNAz-labeled proteins, including intracellular proteins. These data show that the normal distribution of surface glycosylation requires IL-1R, but not MyD88, and is not sufficient to prevent bacterial binding. They also suggest increased P. aeruginosa adhesion to MyD88(-/-) and blotted corneas is not due to reduction in total surface glycosylation, and for tissue paper blotting is likely due to cell permeabilization.-Jolly, A. L., Agarwal, P., Metruccio, M. M. E., Spiciarich, D. R., Evans, D. J., Bertozzi, C. R., Fleiszig, S. M. J. Corneal surface glycosylation is modulated by IL-1R and Pseudomonas aeruginosa challenge but is insufficient for inhibiting bacterial binding.
Chou, Shih-Feng; Lai, Jui-Yang; Cho, Ching-Hsien; Lee, Chih-Hung
Fabrication of the cell spheroids from corneal keratocytes has important implications to the advance in tissue engineering while stimulation from the interface of a biopolymer coating has the ability to modulate this event. This study aims to investigate the dependence of keratocyte migration, proliferation, and differentiation on the surface roughness/stiffness of the chitosan coatings through modifications by degree of deacetylation (DD). After a series of deacetylation process, chitosan coatings with increasing DD exhibited significantly decreased surface roughness and increased surface stiffness. Relationships between the behaviors of rabbit corneal keratocytes (RCKs) and biopolymer coatings with varying DDs (between 75% and 96%) were also found during in vitro cultivation. Both the surface roughness increase and stiffness decrease could lead to enhanced cell migration, which is the main driving force for the early stage spheroid formation on chitosan substrates (e.g., within 8h). With these stimulations from the substrate interfaces, the size and morphology of RCK spheroids were greatly affected by the DD of chitosan. When fabricated on a lowered DD of chitosan material, the spheroids had a larger size with abundant extracellular matrix produced around the cells. At a later stage of spheroid cultivation (e.g., 5 days), significantly higher amount of RCKs on chitosan coatings was noted with increasing DD, indicating the substrate interface effects on cell proliferation. The keratocan expression of RCK spheroids grown on a lowered DD of chitosan was up-regulated, suggesting that both the surface roughness increase and stiffness decrease may facilitate the microenvironment for preservation of cellular phenotype. Overall, our work contributes to the scientific understanding of the keratocyte behaviors and spheroid fabrications in response to DD-mediated surface roughness/stiffness of chitosan coatings. Copyright © 2016 Elsevier B.V. All rights reserved.
Said, Azza Mohamed Ahmed; Farag, Mona Elsayed; Abdulla, Tarek Mohamed; Ziko, Othman Ali Othman; Osman, Wesam Mohamed
AIM To evaluate the effect of punctal occlusion using thermosensitive (smart plug) versus silicone plug for management of aqueous deficient dry eye on corneal sensitivity, ocular surface health and tear film stability. METHODS A comparative prospective interventional case study included 45 patients with bilateral severe form of aqueous deficient dry eye. In each patient, the smart plug was inserted in the lower punctum of the right eye which was considered as study group 1 and silicone plug was inserted in the lower punctum of the left eye of the same patient which was considered as study group 2. All patients were subjected to careful history taking and questionnaire for subjective assessment of severity of symptoms. Corneal sensitivity, corneal fluorescein, rose bengal staining, Schirmer's I test, tear film break up time and conjunctival impression cytology were performed pre and 1, 3 and 6mo post plug insertion. RESULTS A statistically significant improvement in subjective and objective manifestations occurred following treatment with both types of plugs (P<0.01). The thermosensitive plug caused significant overall improvement, decrease in frequency of application of tear substitutes and improvement of conjunctival impression cytology parameters in the inserted side (P<0.01). Canaliculitis was reported in two eyes (4.4%) following punctal occlusion using thermosensitive plug (study group 1). Spontaneous plug loss occurred in 21 eyes (46.6%) in the silicone plug group (study group 2). CONCLUSION Improvement of subjective and objective manifestations of aqueous deficient dry eye occurs following punctal plug occlusion. Thermosensitive plug has good patient's compliance with fewer complications and lower rates of loss compared to the silicone plug. PMID:27990362
Savino, Gustavo; Battendieri, Remo; Riso, Monica; Traina, Salvatore; Poscia, Andrea; DʼAmico, Giovanni; Caporossi, Aldo
To evaluate the corneal topography and the topographic changes after ptosis surgery on patients affected by congenital and acquired blepharoptosis. Twenty eyes of 17 patients affected by acquired and congenital ptosis underwent surgical correction through anterior levator complex tightening. Computerized tomography (Syrius Sistem; CSO) was used to analyze any change in corneal astigmatism (CYL), simulated keratometry, anterior corneal symmetry index front, apical keratometry front, and central corneal thickness. Visual acuity, margin reflex distance, and levator function were also measured. After surgical ptosis repair, corneal topography demonstrated a reduction in average keratometry of 0.15 ± 0.47 diopters (D) and in corneal astigmatism of 0.26 ± 1.12 D. Significant differences were found in apical keratometry front (-1.84 ± 1.76 D) and in best-corrected visual acuity (-0.18 ± 0.06 logMAR) in the postoperative examinations. Central corneal thickness did not show significant differences between preoperative and postoperative examinations. Postoperative topographic maps showed a reduction of symmetry index front (0.10 ± 0.64 D). Eyelid ptosis modifies anterior corneal surface inducing refractive errors and modifying corneal astigmatism in patients, thus affecting the quality of vision. The surgical correction of blepharoptosis induces anterior corneal surface modification, restoring corneal symmetry and regular corneal astigmatism. Postoperative corneal topography showed normal corneal contours.
Belknap, Ellen B
Corneal emergencies can be due to a number of different causes and may be vision threatening if left untreated. In an attempt to stabilize the cornea, it is of benefit to place an Elizabethan collar on the patient to prevent further corneal damage. This article discusses the diagnosis, prognosis, and management of corneal emergencies in dogs and cats. Copyright © 2015 Elsevier Inc. All rights reserved.
Navaratnam, Jesintha; Utheim, Tor P.; Rajasekhar, Vinagolu K.; Shahdadfar, Aboulghassem
Corneal endothelium is a single layer of specialized cells that lines the posterior surface of cornea and maintains corneal hydration and corneal transparency essential for vision. Currently, transplantation is the only therapeutic option for diseases affecting the corneal endothelium. Transplantation of corneal endothelium, called endothelial keratoplasty, is widely used for corneal endothelial diseases. However, corneal transplantation is limited by global donor shortage. Therefore, there is a need to overcome the deficiency of sufficient donor corneal tissue. New approaches are being explored to engineer corneal tissues such that sufficient amount of corneal endothelium becomes available to offset the present shortage of functional cornea. Although human corneal endothelial cells have limited proliferative capacity in vivo, several laboratories have been successful in in vitro expansion of human corneal endothelial cells. Here we provide a comprehensive analysis of different substrates employed for in vitro cultivation of human corneal endothelial cells. Advances and emerging challenges with ex vivo cultured corneal endothelial layer for the ultimate goal of therapeutic replacement of dysfunctional corneal endothelium in humans with functional corneal endothelium are also presented. PMID:26378588
Szekrényesi, Csaba; Sándor, Gábor László; Gyenes, Andrea; Kiss, Huba; Filkorn, Tamás; Nagy, Zoltán
Thermal conditions during photorefractive keratectomy might be an important issue related to the corneal wound healing and long-term outcomes. Authors tried to find out the importance of temperature conditions during the treatment. One eye of 90 patients has been included into the study. Photorefractive keratoctomy was applied with Carl Zeiss MEL 70, MEL 80 and Wavelight Allegretto excimer lasers. EBRO TLC 730 infrared thermometer was used for the measurement of surface temperature of the cornea before epithelial removal, as well as before and after the treatment. Average age of the patients was 25.5 ± 3 yr. Average myopic correction was -3.2 ± 0.8 Dpt. Statistically significant difference was found in temperature change between MEL 80 and the other two types of excimer laser devices. Different air flow conditions of the smoke removal system might have an influence on changes of the corneal temperature during treatment, but the refractive results were not influenced by this issue. Orv. Hetil., 2016, 157(43), 1717-1721.
Lai, Jui-Yang; Tu, I-Hao
In ophthalmology, hyaluronic acid (HA) is an important extracellular matrix (ECM) component and is appropriate for use in generating a microenvironment for cell cultivation. The aim of this work was to evaluate the rabbit corneal keratocyte (RCK) growth in response to HA coatings under serum-free conditions. After modification with HA of varying molecular weights (MWs: 35-1500kDa), the surfaces were characterized by atomic force microscopy and contact angle measurements, and were used for cell culture studies. Our data indicated that the substrates coated with higher negatively charged HA become rougher and are more hydrophilic, resulting in the decrease of cell adhesion and cell-matrix interaction. This early cellular event was likely responsible for the determination of keratocyte configuration. Additionally, for the growth of RCKs on dry HA coatings with surface roughness of 1.1-1.7 nm, a strong cell-cell interaction was observed, which may facilitate the formation of multicellular spheroid aggregates and maintenance of mitotically quiescent state. At each culture time point from 1 to 5 days, a better biosynthetic capacity associated with a higher prevalence of elevated ECM production was found for the cells in a spherical configuration. Irrespective of polysaccharide MW of surface coatings, the RCKs presented good viability without hypoxia-induced death. As compared with a monolayer of adherent keratocytes on tissue culture polystyrene plates and low MW HA-modified samples, the cell spheroids (76-110 μm in diameter) showed significantly higher expressions of keratocan and lumican and lower expressions of biglycan, similar to those of keratocytes in vivo. Moreover, the expression levels of corneal crystallin aldehyde dehydrogenase (7-9-fold increase) and nestin (10-16-fold increase) were greater in larger-sized spheroids, indicating higher ability to maintain cellular transparency and self-renewal potential. It is concluded that the cultured RCKs on surfaces
Majmudar, Parag A; Schallhorn, Steven C; Cason, John B; Donaldson, Kendall E; Kymionis, George D; Shtein, Roni M; Verity, Steven M; Farjo, Ayad A
To review the published literature assessing the efficacy and safety of mitomycin-C (MMC) as an adjunctive treatment in corneal surface excimer laser ablation procedures. Literature searches of the PubMed and Cochrane Library databases were last conducted on August 19, 2014, without language or date limitations. The searches retrieved a total of 239 references. Of these, members of the Ophthalmic Technology Assessment Committee Refractive Management/Intervention Panel selected 26 articles that were considered to be of high or medium clinical relevance, and the panel methodologist rated each article according to the strength of evidence. Ten studies were rated as level I evidence, 5 studies were rated as level II evidence, and the remaining 11 studies were rated as level III evidence. The majority of the articles surveyed in this report support the role of MMC as an adjunctive treatment in surface ablation procedures. When MMC is applied in the appropriate concentration and confined to the central cornea, the incidence of post-surface ablation haze is decreased. Although a minority of studies that evaluated endothelial cell density (ECD) reported an MMC-related decrease in ECD, no clinical adverse outcomes were reported. Over the past 15 years, the use of MMC during surgery in surface ablation has become widespread. There is good evidence of the effectiveness of MMC when used intraoperatively as prophylaxis against haze in higher myopic ablations. Although there are reports of decreased endothelial counts after the administration of MMC during surgery, the clinical significance of this finding remains uncertain, because no adverse outcomes were reported with as much as 5 years of follow-up. Optimal dosage, effectiveness as prophylaxis in lower myopic and hyperopic ablations, and long-term safety, particularly in eyes with reduced corneal endothelial cell counts from prior intraocular surgery, have yet to be established. Copyright © 2015 American Academy of
Cherepnin, A I; Smoliakova, G P; Sorokin, E L
The surface lachrymal-fluid (LF) tension was investigated by teardrop dissection in 115 patients with myopia before they were prescribed soft contact lenses (SCL). Such tension was found to be of clinical importance for the development of SCL adaptation disorders. A longer adaptation period in patients with myopia was associated with a low surface LF tension. A high surface LF tension concurrent with the teardrop dissection mode of the destruction type was typical of the pathological nature of SCL adaptation (12.1% of patients). The obtained data are needed to detect timely the risk of dysadaptation disorders and corneal complications before SCL prescription for the purpose of undertaking the pathogenetically substantiated medication to prevent such complications.
Gruppetta, Steve; Koechlin, Laurent; Lacombe, François; Puget, Pascal
A system to measure the topography of the first optical surface of the human eye noninvasively by using a curvature sensor is described. The static corneal topography and the dynamic topography of the tear film can both be measured, and the topographies obtained are presented. The system makes possible the study of the dynamic aberrations introduced by the tear film to determine their contribution to the overall ocular aberrations in healthy eyes, eyes with corneal pathologies, and eyes wearing contact lenses.
Farid, Marjan; Morishige, Naoyuki; Lam, Larry; Wahlert, Andrew; Steinert, Roger F.; Jester, James V.
Purpose Recent studies have shown that confocal imaging of second harmonic–generated (SHG) signals can detect corneal collagen organization. The purpose of this study was to assess whether SHG signals can detect differences in corneal fibrosis after excimer laser surface ablation (photorefractive keratectomy [PRK]). Methods Rabbits received 9-D PRK in one eye followed by treatment with either mitomycin C (MMC) or vehicle. Corneal haze was measured by in vivo confocal microscopy before and 2, 4, 8, and 12 weeks after surgery. Animals were then killed and corneas were evaluated by visible and nonlinear confocal microscopy. Results PRK induced significant haze in vehicle-treated corneas that peaked at 2 weeks and remained elevated at 12 weeks after surgery. MMC treatment significantly (P = 0.05) reduced corneal haze at 2 weeks and was essentially normal by 12 weeks. Imaging of SHG signals in vehicle-treated eyes showed an anterior layer of collagen forming a honeycomb network blending into a dense mat of irregularly arranged collagen fibers that overlaid normal orthogonally arranged collagen lamellae. MMC treatment showed normal collagen organization at the surface. Fibrotic tissue was associated with a high cell density and alignment of intracellular actin filaments with collagen fiber bundles. In MMC-treated eyes, an anterior acellular zone overlaid a sparsely populated stroma containing isolated and enlarged keratocytes. Conclusions Imaging of SHG signals provides a sensitive means for detection of corneal fibrosis after surface ablation and can be used to assess the effects of antifibrotic therapy on corneal healing after refractive surgery. PMID:18502995
Lin, David Pei-Cheng; Chang, Han-Hsin; Yang, Li-Chien; Huang, Tzu-Ping; Liu, Hsiang-Jui; Chang, Lin-Song; Lin, Chien-Hsun
Purpose Weekly disposable soft contact lenses have been widely used recently, but their shield effects against ultraviolet (UV) irradiation remain to be evaluated. This study investigated the bioprotective effects of several weekly soft contact lenses against UVB irradiation on the corneal surface in a mouse model. Methods Fifty ICR mice were randomly divided into five groups: (1) blank control, (2) exposed to UVB without contact lens protection, (3) exposed to UVB and protected with Vifilcon A contact lenses, (4) exposed to UVB and protected with Etafilcon A contact lenses, and (5) exposed to UVB and protected with HEMA+MA contact lenses. The exposure to UVB irradiation was performed at 0.72 J/cm2/day after anesthesia for a 7-day period, followed by cornea surface assessment for smoothness, opacity, and grading of lissamine green staining. Tissue sections were prepared for hematoxylin and eosin staining and immunohistochemical detection by using antibodies against myeloperoxidase, cytokeratin-5, P63, Ki-67, nuclear factor-kappa B (p65), cyclooxygenase-2, Fas L, and Fas. Results The results showed impaired corneal surface with myeloperoxidase+ polymorphonuclear leukocyte infiltration into the stroma after UVB exposure, in contrast to the intact status of the blank controls. The corneas with Etafilcon A and HEMA+MA contact lenses maintained more cells positive for cytokeratin-5, P63, and Ki-67 compared to those with Vifilcon A or without contact lens protection. Furthermore, less proinflammatory factors, including nuclear factor-kappa (p65), cyclooxygenase-2, Fas L, and Fas, were induced in the corneas protected by Etafilcon A and HEMA+MA. Conclusions This study demonstrated various protective effects of weekly disposable contact lenses against UVB irradiation. The mouse model used in the present study may be used extensively for in vivo assessment of UV shield efficacy. PMID:23734085
Cejkova, Jitka; Trosan, Peter; Cejka, Cestmir; Lencova, Anna; Zajicova, Alena; Javorkova, Eliska; Kubinova, Sarka; Sykova, Eva; Holan, Vladimir
The purpose of this study was to investigate whether rabbit bone marrow-derived mesenchymal stem cells (MSCs) effectively decrease alkali-induced oxidative stress in the rabbit cornea. The alkali (0.15 N NaOH) was applied on the corneas of the right eyes and then rinsed with tap water. In the first group of rabbits the injured corneas remained untreated. In the second group MSCs were applied on the injured corneal surface immediately after the injury and eyelids sutured for two days. Then the sutures were removed. In the third group nanofiber scaffolds seeded with MSCs (and in the fourth group nanofibers alone) were transferred onto the corneas immediately after the injury and the eyelids sutured. Two days later the eyelid sutures were removed together with the nanofiber scaffolds. The rabbits were sacrificed on days four, ten or fifteen after the injury, and the corneas were examined immunohistochemically, morphologically, for the central corneal thickness (taken as an index of corneal hydration) using an ultrasonic pachymeter and by real-time PCR. Results show that in untreated injured corneas the expression of malondialdehyde (MDA) and nitrotyrosine (NT) (important markers of lipid peroxidation and oxidative stress) appeared in the epithelium. The antioxidant aldehyde dehydrogenase 3A1 (ALDH3A1) decreased in the corneal epithelium, particularly in superficial parts, where apoptotic cell death (detected by active caspase-3) was high. (In control corneal epithelium MDA and NT are absent and ALDH3A1 highly present in all layers of the epithelium. Cell apoptosis are sporadic). In injured untreated cornea further corneal disturbances developed: The expressions of matrix metalloproteinase 9 (MMP9) and proinflammatory cytokines, were high. At the end of experiment (on day 15) the injured untreated corneas were vascularized and numerous inflammatory cells were present in the corneal stroma. Vascular endothelial growth factor (VEGF) expression and number of macrophages
He, Ji C.; Gwiazda, Jane; Thorn, Frank; Held, Richard
In order to investigate the sources of wave-front aberrations in the human eye, we have measured the aberrations of the anterior cornea and the whole eye using a topographic system and a psychophysical wave-front sensor. We have also calculated the aberrations for the internal optics of both eyes of 45 young subjects (aged 9 to 29 years). The mean rms for the anterior cornea was similar to that for the internal optics and the whole eye when astigmatism was included, but less than that for both the internal optics and the whole eye with astigmatism removed. For eyes with low whole-eye rms values, mean rms for the anterior cornea was greater than that for the whole eye, suggesting that the anterior corneal aberration is partially compensated by the internal optics of the eye to produce the low whole-eye rms. For eyes with larger whole-eye rms values, the rms values for both the anterior cornea and the internal optics were less than that for the whole eye. Thus the aberrations for the two elements tend to be primarily additive. This pattern exists whether or not astigmatism was included in the wave-front aberration rms. For individual Zernike terms, astigmatism and spherical aberration in the anterior cornea were partially compensated by internal optics, while some other Zernike terms showed addition between the anterior cornea and internal optics. Individual eyes show different combinations of compensation and addition across different Zernike terms. Our data suggest that the reported loss of internal compensation for anterior corneal aberrations in elderly eyes with large whole-eye aberrations J. Opt. Soc. Am. A 19 , 137 (2002) may also occur in young eyes. 2003 Optical Society of America
Wei, Shufang; Zhang, Cuiying; Zhang, Shaoru; Xu, Yanyun; Mu, Guoying
To study the treatment effect of corneal collagen cross-linking (CXL) combined with 440 nm blue light and riboflavin on bacterial corneal ulcer using animal experiments. A total of 21 New Zealand white rabbits that developed Staphylococcus aureus corneal ulcer were randomly divided into three groups. Seven rabbits were used as blank control groups; seven rabbits were treated with CXL combined with riboflavin and 440 nm blue light; and seven rabbits were treated with CXL combined with riboflavin and 370 nm ultraviolet A light. Necrotic tissues or secretions from the ulcer surface, eye secretions, conjunctival hyperemia, hypopyon, corneal infiltration, and pathological changes of the cornea were all observed. The 1st, 3th, and 7th day after CXL treatment, a statistically significant difference was found among the inflammation scores of the three groups. The scores of 440 and 370 groups decreased gradually, significantly lower than that of the control group. Bacterial cultures of 440 and 370 groups turned to be negative while that of the control group remained positive. After 1 day of CXL treatment, pathology pictures of the three groups all showed loss of corneal epithelia with many inflammatory cells in deep stroma. After 7 days of CXL treatment, abscess formed in almost all corneal area in the control group, while in 440 and 370 groups, multilayer healing of corneal epithelia, neovascularization, and many inflammatory cells within ulcers and proliferation of a small amount of fibroblast were seen. CXL combined with riboflavin and 440 nm blue light is effective in treating S. aureus corneal ulcer.
... as sand or dust Ultraviolet injuries: Caused by sunlight, sun lamps, snow or water reflections, or arc- ... a corneal injury if you: Are exposed to sunlight or artificial ultraviolet light for long periods of ...
... Causes a Corneal Abrasion? Your eye has other defenses besides the orbital bone: The eyelids and eyelashes ... The Nemours Foundation, iStock, Getty Images, Corbis, Veer, Science Photo Library, Science Source Images, Shutterstock, and Clipart. ...
... lenses to achieve the best vision. Laser vision correction may be an option if you have nearsightedness, ... Editorial team. Related MedlinePlus Health Topics Corneal Disorders Refractive Errors Browse the Encyclopedia A.D.A.M., Inc. ...
... fingernails short, too.Use care when putting in contact lenses. Make sure you clean them properly each day.Don’t sleep in your contact lenses.Trim low-hanging tree branches. Corneal abrasion treatment ...
Zarranz Ventura, J; De Nova, E; Moreno-Montañés, J
Systemic diseases affecting the cornea have a wide range of manifestations. The detailed study of all pathologies that cause corneal alteration is unapproachable, so we have centered our interest in the most prevalent or characteristic of them. In this paper we have divided these pathologies in sections to facilitate their study. Pulmonar and conective tissue (like colagen, rheumatologic and idiopathic inflamatory diseases), dermatologic, cardiovascular, hematologic, digestive and hepatopancreatic diseases with corneal alteration are described. Endocrine and metabolic diseases, malnutrition and carential states are also studied, as well as some otorhinolaryngologic and genetic diseases that affect the cornea. Finally, a brief report of ocular toxicity induced by drugs is referred.
Zainuddin; Chirila, Traian V.; Barnard, Zeke; Watson, Gregory S.; Toh, Chiong; Blakey, Idriss; Whittaker, Andrew K.; Hill, David J. T.
Physical and chemical changes at the surface of poly(2-hydroxyethyl methacrylate) (PHEMA) hydrogels modified by ablation with an F 2 excimer laser were investigated experimentally. An important observation was that only the outer exposed surface layers of the hydrogel were affected by the exposure to 157 nm radiation. The effect of the surface changes on the tendency of cells to adhere to the PHEMA was also investigated. A 0.5 cm 2 area of the hydrogel surfaces was exposed to laser irradiation at 157 nm to fluences of 0.8 and 4 J cm -2. The changes in surface topography were analysed by light microscopy and atomic force microscopy, while the surface chemistry was characterized by attenuated total reflection infrared and X-ray photoelectron spectroscopies. Cell-interfacial interactions were examined based on the proliferation of human corneal limbal epithelial (HLE) cells cultured on the laser-modified hydrogels, and on the unexposed hydrogels and tissue culture plastic for comparison. It was observed that the surface topography of laser-exposed hydrogels showed rippled patterns with a surface roughness increasing at the higher exposure dose. The changes in surface chemistry were affected not only by an indirect effect of hydrogen and hydroxyl radicals, formed by water photolysis, on the PHEMA, but also by the direct action of laser radiation on PHEMA if the surface layers of the gel become depleted of water. The laser treatment led to a change in the surface characteristics, with a lower concentration of ester side-chains and the formation of new oxygenated species at the surface. The surface also became more hydrophobic. Most importantly, the surface chemistry and the newly created surface topographical features were able to improve the attachment, spreading and growth of HLE cells.
Klyce, Stephen D.; Wilson, Steven E.
The cornea is the major refractive element in the eye; even minor surface distortions can produce a significant reduction in visual acuity. Standard clinical methods used to evaluate corneal shape include keratometry, which assumes the cornea is ellipsoidal in shape, and photokeratoscopy, which images a series of concentric light rings on the corneal surface. These methods fail to document many of the corneal distortions that can degrade visual acuity. Algorithms have been developed to reconstruct the three dimensional shape of the cornea from keratoscope images, and to present these data in the clinically useful display of color-coded contour maps of corneal surface power. This approach has been implemented on a new generation video keratoscope system (Computed Anatomy, Inc.) with rapid automatic digitization of the image rings by a rule-based approach. The system has found clinical use in the early diagnosis of corneal shape anomalies such as keratoconus and contact lens-induced corneal warpage, in the evaluation of cataract and corneal transplant procedures, and in the assessment of corneal refractive surgical procedures. Currently, ray tracing techniques are being used to correlate corneal surface topography with potential visual acuity in an effort to more fully understand the tolerances of corneal shape consistent with good vision and to help determine the site of dysfunction in the visually impaired.
Willcox, Mark; Sharma, Savitri; Naduvilath, Thomas J; Sankaridurg, Padmaja R; Gopinathan, Usha; Holden, Brien A
To determine whether carriage of microbes on the contact lens or ocular surfaces during extended wear (EW) with soft hydroxyethyl methacrylate (HEMA)-based contact lenses predisposes the wearer to adverse events. Participants (non-contact lens wearers) were enrolled in a clinical study involving wear of HEMA-based hydrogel lenses on a six night EW basis with weekly replacement. Type and number of bacteria colonizing the lower lid margins, upper bulbar conjunctiva, and contact lenses during EW after one night, 1 week, 1 month, and thereafter every 3 months for 3.5 years were determined. The association of bacteria with adverse responses was compared between carriers (defined as having significant microbes cultured from two or more samples with 1 year) and noncarriers, and the strength of the association was estimated using multivariate logistic regression. Carriers of gram-positive bacteria on lenses (particularly coagulase negative staphylococci or Corynebacterium spp.) were approximately three and eight times more likely to develop contact lens-induced peripheral ulcers (CLPUs) and asymptomatic infiltrates (AIs), respectively. Staphylococcus aureus was most frequently isolated from lenses during CLPU. Carriers of gram-negative bacteria on lenses were five times more likely to develop contact lens-induced acute red eye (CLARE). Haemophilus influenzae was isolated most frequently from lenses during CLARE and AI events. Bacterial carriage on contact lenses during EW predisposes the wearer to the development of corneal inflammatory events including CLARE, CLPU, and AI.
Alnawaiseh, Maged; Zumhagen, Lars; Wirths, Gabriele; Eveslage, Maria; Eter, Nicole; Rosentreter, André
The aim of the study was to quantify Scheimpflug corneal densitometry in patients with Fuchs endothelial dystrophy (FED). In this study, we retrospectively reviewed the charts and anterior segment data of 49 patients with FED before posterior lamellar keratoplasty and 51 healthy controls. The patients were examined using the Scheimpflug-based Oculus Pentacam. Central corneal thickness (CCT), ring-averaged (on a circle of 2, 2.4-10 mm diameter) noncentral corneal thickness, and densitometry data in different corneal layers and in different annuli were extracted and analyzed. The total corneal light backscatter at total corneal thickness (CT) and at total diameter was significantly higher in the FED group when compared with the control group (FED group: 28.8 ± 6.7; control group: 24.3 ± 4.1; P < 0.001). When the corneal surface was divided into concentric annular zones at total CT, the differences were significant only in the 2 central annuli (P < 0.001). The total corneal light backscatter at total CT in the central 0-2 mm annulus correlated moderately with the central corneal thickness (Pearson's correlation = 0.55, P < 0.001). Corneal light backscatter in the central cornea was greater in patients with FED than in normal subjects. Corneal densitometry enables us to evaluate the optical quality of the cornea in different corneal layers and in different annuli. It is a useful, objective method that, in combination with central corneal thickness and corneal central-to-peripheral thickness ratio, can help to quantify FED severity.
Wang, Li-Ke; Huang, Yan-Ping; Tian, Lei; Kee, Chea-Su; Zheng, Yong-Ping
Biomechanical properties are potential information for the diagnosis of corneal pathologies. An ultrasound indentation probe consisting of a load cell and a miniature ultrasound transducer as indenter was developed to detect the force-indentation relationship of the cornea. The key idea was to utilize the ultrasound transducer to compress the cornea and to ultrasonically measure the corneal deformation with the eyeball overall displacement compensated. Twelve corneal silicone phantoms were fabricated with different stiffness for the validation of measurement with reference to an extension test. In addition, fifteen fresh porcine eyes were measured by the developed system in vitro. The tangent moduli of the corneal phantoms calculated using the ultrasound indentation data agreed well with the results from the tensile test of the corresponding phantom strips (R(2)=0.96). The mean tangent moduli of the porcine corneas measured by the proposed method were 0.089±0.026MPa at intraocular pressure (IOP) of 15mmHg and 0.220±0.053MPa at IOP of 30mmHg, respectively. The coefficient of variation (CV) and intraclass correlation coefficient (ICC) of tangent modulus were 14.4% and 0.765 at 15mmHg, and 8.6% and 0.870 at 30mmHg, respectively. The preliminary study showed that ultrasound indentation could be applied to the measurement of corneal tangent modulus with good repeatability and improved measurement accuracy compared to conventional surface displacement-based measurement method. The ultrasound indentation can be a potential tool for the corneal biomechanical properties measurement in vivo.
Rajan, M S
The recent years have brought about a sea change in the field of corneal transplantation with penetrating keratoplasty being phased to newer lamellar keratoplasty techniques for a variety of corneal pathology. Improved and innovative surgical techniques have allowed selective replacement of diseased host corneal layers with pre-prepared healthy donor corneal lamellae for anterior corneal disorders such as keratoconus and posterior corneal disorders such as Fuch's corneal endothelial dystrophy. The results of lamellar techniques are encouraging, with rapid visual rehabilitation and vastly reduced risk of immune-mediated transplant rejection. The techniques of deep anterior lamellar keratoplasty and Descemet's stripping endothelial keratoplasty (DSAEK) continue to evolve with advent of femtosecond lasers and newer concepts such as pre-conditioned donor corneas for Microthin DSAEK and Descemet's membrane keratoplasty. This review describes the current developments in lamellar keratoplasty, including the futuristic approach using cell therapy to restore vision in corneal blindness. PMID:24384964
Mimura, Tatsuya; Yokoo, Seiichi; Yamagami, Satoru
Human corneal endothelial cells (HCECs) do not replicate after wounding. Therefore, corneal endothelial deficiency can result in irreversible corneal edema. Descemet stripping automated endothelial keratoplasty (DSAEK) allows selective replacement of the diseased corneal endothelium. However, DSAEK requires a donor cornea and the worldwide shortage of corneas limits its application. This review presents current knowledge on the tissue engineering of corneal endothelium using cultured HCECs. We also provide our recent work on tissue engineering for DSAEK grafts using cultured HCECs. We reconstructed DSAEK grafts by seeding cultured DiI-labelled HCECs on collagen sheets. Then HCEC sheets were transplanted onto the posterior stroma after descemetorhexis in the DSAEK group. Severe stromal edema was detected in the control group, but not in the DSAEK group throughout the observation period. Fluorescein microscopy one month after surgery showed numerous DiI-labelled cells on the posterior corneal surface in the DSAEK group. Frozen sections showed a monolayer of DiI-labelled cells on Descemet’s membrane. These findings indicate that cultured adult HCECs, transplanted with DSAEK surgery, maintain corneal transparency after transplantation and suggest the feasibility of performing DSAEK with HCECs to treat endothelial dysfunction. PMID:24955745
Dutescu, R Michael; Panfil, Claudia; Schrage, Norbert
Ingredients of lubricant eye drops are potentially harmful to the ocular surface. The products Optive, Optive Fusion, Neopt were tested regarding corneal irritability versus Vismed Multi and 0.01% benzalkonium chloride as negative and positive control, respectively. Formulas (30-40μl per hour) were applied hourly in-vitro for six days on rabbit corneas (n=5, per product) cultured in artificial anterior chambers (EVEIT system). Initially, four corneal abrasions (2.4-4.6mm(2)) were induced. All defects were monitored during drop application by fluorescein stains and photographs. To ensure corneal vitality, glucose and lactate concentrations in artificial anterior chamber fluids were determined photometrically. All products showed a complete corneal healing on day 2. Thereafter, all five Optive-treated corneas developed progressive fluorescein-positive epithelial lesions until day six (24.96μm, ±21.45μm, p<0.01). For Optive Fusion three corneas showed corneal erosions on day six (23.11μm, ±37.02μm, p>0.5) while Vismed Multi did not adversely affect the corneal integrity. Glucose/lactate concentrations remained unchanged while lubricants were applied. Histology revealed epithelial loss and severe alterations of the superficial stroma for Optive. Optive Fusion displayed a comparable pathology. Neopt did not significantly affect the corneal healing and integrity. This study suggested a cumulative corneal toxicity of Optive and, to a lesser extent, Optive Fusion most likely caused by its oxidative preservative, SOC. Clinical data are needed to clarify the application frequency at which corneal toxicity might occur. Neopt and Vismed Multi did not affect the corneal integrity. Copyright © 2016 Elsevier GmbH. All rights reserved.
Petznick, Andrea; Madigan, Michele C; Garrett, Qian; Sweeney, Deborah F; Evans, Margaret D M
This study investigated ocular surface components that contribute to matrix-metalloproteinase (MMP)-2 and MMP-9 found in tears following corneal epithelial wounding. Laboratory short-haired cats underwent corneal epithelial debridement in one randomly chosen eye (n = 18). Eye-flush tears were collected at baseline and during various healing stages. Procedural control eyes (identical experimental protocol as wounded eyes except for wounding, n = 5) served as controls for tear analysis. MMP activity was analyzed in tears using gelatin zymography. MMP staining patterns were evaluated in ocular tissues using immunohistochemistry and used to determine MMP expression sites responsible for tear-derived MMPs. The proMMP-2 and proMMP-9 activity in tears was highest in wounded and procedural control eyes during epithelial migration (8 to 36 hours post-wounding). Wounded eyes showed significantly higher proMMP-9 in tears only during and after epithelial restratification (day 3 to 4 and day 7 to 28 post-wounding, respectively) as compared to procedural controls (p<0.05). Tears from wounded and procedural control eyes showed no statistical differences for pro-MMP-2 and MMP-9 (p>0.05). Immunohistochemistry showed increased MMP-2 and MMP-9 expression in the cornea during epithelial migration and wound closure. The conjunctival epithelium exhibited highest levels of both MMPs during wound closure, while MMP-9 expression was reduced in conjunctival goblet cells during corneal epithelial migration followed by complete absence of the cells during wound closure. The immunostaining for both MMPs was elevated in the lacrimal gland during corneal healing, with little/no change in the meibomian glands. Conjunctival-associated lymphoid tissue (CALT) showed weak MMP-2 and intense MMP-9 staining. Following wounding, migrating corneal epithelium contributed little to the observed MMP levels in tears. The major sources assessed in the present study for tear-derived MMP-2 and MMP-9
Myrna, Kathern E.; Mendonsa, Rima; Russell, Paul; Pot, Simon A.; Liliensiek, Sara J.; Jester, James V.; Nealey, Paul F.; Brown, Donald
Purpose. The transition of corneal fibroblasts to the myofibroblast phenotype is known to be important in wound healing. The purpose of this study was to determine the effect of topographic cues on TGFβ-induced myofibroblast transformation of corneal cells. Methods. Rabbit corneal fibroblasts were cultured on nanopatterned surfaces having topographic features of varying sizes. Cells were cultured in media containing TGFβ at concentrations ranging from 0 to 10 ng/mL. RNA and protein were collected from cells cultured on topographically patterned and planar substrates and analyzed for the myofibroblast marker α-smooth muscle actin (αSMA) and Smad7 expression by quantitative real time PCR. Western blot and immunocytochemistry analysis for αSMA were also performed. Results. Cells grown on patterned surfaces demonstrated significantly reduced levels of αSMA (P < 0.002) compared with planar surfaces when exposed to TGFβ; the greatest reduction was seen on the 1400 nm surface. Smad7 mRNA expression was significantly greater on all patterned surfaces exposed to TGFβ (P < 0.002), whereas cells grown on planar surfaces showed equal or reduced levels of Smad7. Western blot analysis and αSMA immunocytochemical staining demonstrated reduced transition to the myofibroblast phenotype on the 1400 nm surface when compared with cells on a planar surface. Conclusions. These data demonstrate that nanoscale topographic features modulate TGFβ-induced myofibroblast differentiation and αSMA expression, possibly through upregulation of Smad7. It is therefore proposed that in the wound environment, native nanotopographic cues assist in stabilizing the keratocyte/fibroblast phenotype while pathologic microenvironmental alterations may be permissive for increased myofibroblast differentiation and the development of fibrosis and corneal haze. PMID:22232431
Myrna, Kathern E; Mendonsa, Rima; Russell, Paul; Pot, Simon A; Liliensiek, Sara J; Jester, James V; Nealey, Paul F; Brown, Donald; Murphy, Christopher J
The transition of corneal fibroblasts to the myofibroblast phenotype is known to be important in wound healing. The purpose of this study was to determine the effect of topographic cues on TGFβ-induced myofibroblast transformation of corneal cells. Rabbit corneal fibroblasts were cultured on nanopatterned surfaces having topographic features of varying sizes. Cells were cultured in media containing TGFβ at concentrations ranging from 0 to 10 ng/mL. RNA and protein were collected from cells cultured on topographically patterned and planar substrates and analyzed for the myofibroblast marker α-smooth muscle actin (αSMA) and Smad7 expression by quantitative real time PCR. Western blot and immunocytochemistry analysis for αSMA were also performed. Cells grown on patterned surfaces demonstrated significantly reduced levels of αSMA (P < 0.002) compared with planar surfaces when exposed to TGFβ; the greatest reduction was seen on the 1400 nm surface. Smad7 mRNA expression was significantly greater on all patterned surfaces exposed to TGFβ (P < 0.002), whereas cells grown on planar surfaces showed equal or reduced levels of Smad7. Western blot analysis and αSMA immunocytochemical staining demonstrated reduced transition to the myofibroblast phenotype on the 1400 nm surface when compared with cells on a planar surface. These data demonstrate that nanoscale topographic features modulate TGFβ-induced myofibroblast differentiation and αSMA expression, possibly through upregulation of Smad7. It is therefore proposed that in the wound environment, native nanotopographic cues assist in stabilizing the keratocyte/fibroblast phenotype while pathologic microenvironmental alterations may be permissive for increased myofibroblast differentiation and the development of fibrosis and corneal haze.
Ishihara, Miya; Arai, Tsunenori; Sato, Shunichi; Morimoto, Yuji; Obara, Minoru; Kikuchi, Makoto
We have developed the fast time-response measurement of thermal radiation with 15ns rise time to monitor the corneal surface temperature during ArF excimer laser ablation. In this study, e aim to investigate the influence of the relation between the corneal penetration depth and sampling depth of the measurement system on the measured temperature using 193 nm and 247 nm pulsed lights which have different penetration depths of cornea. When the sampling depth was defined as the penetration depth of cornea at the thermal radiation wavelength, we obtained about 3 micrometers of the sampling depth by pulsed photothermal radiometry (PPTR). In the case of the 247 nm light irradiation, where the corneal absorption coefficient at 247 nm was approximately equal to that for the thermal radiation, we found that the measured temperature rises were same as the estimated temperature rises based on the photothermal process. In contrast, in the case of the 193 nm light irradiation, where the absorption coefficient at 193 nm was larger than that for the thermal radiation, we found that the measured temperature rises were lower than the estimated temperature rises.
Sunny, M C; Sharma, C P
Polymers like poly(methylmethacrylate) (PMMA) and poly(2-hydroxyethylmethacrylate) (PHEMA) are widely used in the development of hard and soft contact lenses. Cell adhesion and deposition of chemicals such as calcium, lipoproteins and mucin on the lens surface cause visual acuity which is the main problem in extended uses of contact ocular lenses. In order to minimise the cell adhesion and other type of depositions, a method of surface modification of lens involving the use of phosphoryl choline, a phospholipid and the glow discharge technique has been described. The power variation of the lenses after modification has been checked using Topcon lensometer. The possible power changes of the modified samples due to the exposure to the normal light in the laboratory, darkness, ultraviolet (U.V.) light or saline have been investigated by taking the visible and ultra violet spectra using Beckman spectrophotometer. Surface energy variations after modifications of the samples have been checked by sessile drop water contact angle measurements. Glow discharge treatment increases the hydrophilicity of the samples. It seems, the modifications do not affect the power of hard contact lens significantly. It is also observed that the exposure of samples to the normal light in the laboratory, darkness, U.V. light or saline make no significant change in the visible and ultraviolet spectra of the samples before and after modification.
Yanai, Kaori; Huang, Jane; Kadonosono, Kazuaki; Uchio, Eiichi
To evaluate the safety of bromfenac sodium eye drops from the standpoint of corneal sensitivity and tear secretion in healthy controls following instillation for 1 month. A prospective single-blind parallel clinical study was conducted in 20 eyes of ten healthy volunteers with no history of ocular or systemic allergic disease, dry eye, contact lens wear, or ocular surgery. Participants were instructed to instill either bromfenac sodium or artificial tears in each eye twice daily for 28 days. Corneal sensitivity tested using a Cochet-Bonnet esthesiometer was evaluated before and immediately after instillation at 7, 14, and 28 days after the initiation of treatment. Tear secretion was also evaluated by Schirmer's eye test before and at 28 days. No significant difference in mean corneal sensitivity and tear-secretion rate was observed between the bromfenac and artificial-tear treatment groups at any time. These results indicate that bromfenac sodium eye drops are safe with respect to corneal sensitivity and tear secretion in subjects with a normal ocular surface condition. Further evaluation is still necessary to determine whether bromfenac is safe in pathological conditions, such as inflammatory disorders and postsurgical cases.
Zernii, E Yu; Gancharova, O S; Ishutina, I E; Baksheeva, V E; Golovastova, M O; Kabanova, E I; Savchenko, M S; Serebryakova, M V; Sotnikova, L F; Zamyatnin, A A; Philippov, P P; Senin, I I
Perioperative corneal abrasion is an ophthalmic complication commonly found in patients underwent general anesthesia. In this study, correlations between development of corneal injury and proteomic changes in tear film during general anesthesia were examined using an animal (rabbit) model. Being started after 1-h anesthesia, the process of accumulation of pathological changes in the cornea unequivocally led clinically significant abrasions following 3-6 h of the narcosis. The corneal damage was associated with alterations in profiles of major proteins of the tear film. Analysis of the tear proteome pointed to depression of lachrymal glands function, and suggested serotransferrin, serum albumin and annexin A1 as potential tear markers of the complication. The tear film alterations included fast drop of total antioxidant activity and activity of superoxide dismutase, and decrease in interleukin-4 and increase in interleukin-6 content indicating development of oxidative and pro-inflammatory responses. These findings suggest antioxidant and anti-inflammatory therapy as prospective approach for prevention/treatment of perioperative corneal abrasions. The observed anesthesia-induced effects should be considered in any study of ocular surface diseases employing anesthetized animals.
To report a rare case of corneal honeybee sting. The corneal honeybee stinger was removed under slit-lamp guidance using a 27-gauge needle. Corneal edema resolved by 90% the next day after removal of the honeybee stinger without using topical steroids. The patient's condition improved significantly after removal of the corneal honeybee stinger, and corneal edema disappeared. The patient was evaluated in 1 week and then 3 months with permanent mild central corneal opacity.
Degenerative or hereditary corneal diseases are sometimes difficult to discriminate. Corneal dystrophies affect approximately 0.09 % of the population. They are identified by the IC3D classification based on their phenotype, genotype and evidence gathered for their diagnosis. Practically, the ophthalmologist manages functional symptoms, such as recurrent erosions, visual loss and amblyopia, photophobia, foreign body sensation, and sometimes pain and aesthetic concerns. Medical treatments consist of drops to promote healing, ointments, hyperosmotic agents and bandage contact lenses. Less invasive surgical treatments are used as second line therapy (phototherapeutic keratectomy, lamellar keratectomy). More invasive procedures may eventually be utilized (lamellar or penetrating keratoplasty). Anterior lamellar or endothelial keratoplasty are now preferred to penetrating keratoplasty, although the latter still remains the only possible option in some cases. Some rare dystrophies require coordinated and comprehensive medical care. Copyright © 2017 Elsevier Masson SAS. All rights reserved.
Degenerative or hereditary corneal diseases are sometimes difficult to discriminate. Corneal dystrophies affect approximately 0.09% of the population. They are identified by the IC3D classification based on their phenotype, genotype and evidence gathered for their diagnosis. In practice, the ophthalmologist manages functional symptoms such as recurrent erosions, visual loss and amblyopia, photophobia, foreign body sensation, and sometimes pain and aesthetic concerns. Medical treatments consist of drops to promote healing, ointments, hyperosmotic agents and bandage contact lenses. Less invasive surgical treatments are used as second line therapy (phototherapeutic keratectomy, lamellar keratectomy). More invasive procedures may eventually be utilized (lamellar or penetrating keratoplasty). Anterior lamellar or endothelial keratoplasty are now preferred to penetrating keratoplasty, although the latter still remains the only possible option in some cases. Some rare dystrophies require coordinated and comprehensive medical care. Copyright © 2017 Elsevier Masson SAS. All rights reserved.
Krachmer, J H; Feder, R S; Belin, M W
Keratoconus and other noninflammatory corneal thinning disorders (keratoglobus, pellucid marginal degeneration and posterior keratoconus) are characterized by progressive corneal thinning, protrusion and scarring; the result is distorted and decreased vision. The etiology and pathogenesis of these disorders are unknown but may be associated with a variety of factors, including contact lens wear, eye rubbing, Down's syndrome, atopic disease, connective tissue disease, tapetoretinal degeneration and inheritance. Recent advances in techniques for biochemical and pathological investigation are now allowing further exploration in these areas. Early diagnosis is aided by the finding of irregular corneal astigmatism with inferior corneal steepening. Treatment ranges from simple spectacle correction to keratoplasty. In this review, the past and present literature on corneal thinning disorders is reviewed and practical approaches to diagnosis and management are outlined.
Abdelfattah, Nizar Saleh; Amgad, Mohamed; Zayed, Amira A; Salem, Hamdy; Elkhanany, Ahmed E; Hussein, Heba; Abd El-Baky, Nawal
A large subset of corneal pathologies involves the formation of new blood and lymph vessels (neovascularization), leading to compromised visual acuity. This article aims to review the clinical causes and presentations of corneal neovascularization (CNV) by examining the mechanisms behind common CNV-related corneal pathologies, with a particular focus on herpes simplex stromal keratitis, contact lenses-induced keratitis and CNV secondary to keratoplasty. Moreover, we reviewed CNV in the context of different types of corneal transplantation and keratoprosthesis, and summarized the most relevant treatments available so far. PMID:25709930
Moore, Phillip Anthony
The cornea is naturally transparent. Anything that interferes with the cornea's stromal architecture, contributes to blood vessel migration, increases corneal pigmentation, or predisposes to corneal edema, disrupts the corneas transparency and indicates corneal disease. The color, location, and shape and pattern of a corneal lesion can help in determining the underlying cause for the disease. Corneal disease is typically divided into congenital or acquired disorders. Congenital disorders, such as corneal dermoids are rare in cats, whereas acquired corneal disease associated with nonulcerative or ulcerative keratitis is common. Primary ocular disease, such as tear film instability, adenexal disease (medial canthal entropion, lagophthalmus, eyelid agenesis), and herpes keratitis are associated with the majority of acquired corneal disease in cats. Proliferative/eosinophilic keratitis, acute bullous keratopathy, and Florida keratopathy are common feline nonulcerative disorders. Nonprogressive ulcerative disease in cats, such as chronic corneal epithelial defects and corneal sequestration are more common than progressive corneal ulcerations.
Deshpande, Pallavi; Ramachandran, Charanya; Sefat, Farshid; Mariappan, Indumathi; Johnson, Claire; McKean, Robert; Hannah, Melanie; Sangwan, Virender S; Claeyssens, Frederik; Ryan, Anthony J; MacNeil, Sheila
Currently, damage to the ocular surface can be repaired by transferring laboratory cultured limbal epithelial cells (LECs) to the cornea using donor human amniotic membrane as the cell carrier. We describe the development of a synthetic biodegradable membrane of Poly D,L-lactide-co-glycolide (PLGA) with a 50:50 ratio of lactide and glycolide for the delivery of both isolated LECs and of cells grown out from limbal tissue explants. Both isolated LECs and limbal explants produced confluent limbal cultures within 2 weeks of culture on the membranes without the need for fibroblast feeder layers. Outgrowth of cells from explants was promoted by the inclusion of fibrin. Membranes with cells on them broke down predictably within 4-6 weeks in vitro and the breakdown was faster for a lower molecular weight (MW) (44 kg/mol) rather than a higher MW (153 kg/mol) PLGA. Membranes could be reproducibly produced, sterilised with gamma irradiation and stored dry at -20 °C for at least 12 months, and the ability to support cell outgrowth from explants was retained. We demonstrate transfer of cells (both isolated LECs and of cells grown out from limbal explants) from the membranes to an ex vivo rabbit cornea model. Characterisations of the cells by immunohistochemistry showed both differentiated and stem cell populations. A synthetic membrane combined with limbal explants in theatre would avoid the need for tissue banked human amniotic membrane and also avoid the need for specialist laboratory facilities for LEC expansion making this more accessible to many more surgeons and patients.
Nakamura, Yoshikuni; Nakamura, Takahiro; Tarui, Takeshi; Inoue, Jun; Kinoshita, Shigeru
The peroxisome proliferator-activated receptor (PPAR) δ is involved in tissue repair. In this study, we investigated the functional role of PPARδ in corneal epithelial wound healing. In an in vivo corneal wound-healing model, the changes of PPARδ expression in corneal epithelia were examined by immunofluorescence microscopy, and the effect of topical administrations of a PPARδ agonist on corneal wound healing was also evaluated. The inhibitory effect of a PPARδ agonist on the cytokine-induced death of human corneal epithelial cells was evaluated using a DNA fragmentation assay kit. The changes of PPARδ expression and epithelial cell death were also investigated using human corneoscleral tissues ex vivo. Our findings showed that PPARδ expression was temporally up-regulated in corneal epithelial cells during experimental wound healing and that topical administration of a PPARδ agonist significantly promoted the healing of experimental corneal epithelial wounds. In human corneal epithelial cells, up-regulation of PPARδ and DNA fragmentation was demonstrated by stimulation with cytokines, and the DNA fragmentation was significantly inhibited by pretreatment with a PPARδ agonist. By using human corneoscleral tissues ex vivo, PPARδ was up-regulated in both healthy corneal epithelia (during re-epithelialization) and diseased corneal epithelia. Inflammatory stimulation-induced corneal epithelial cell death was inhibited by pretreatment with a PPARδ agonist. These results strongly suggest that PPARδ is involved in the corneal epithelial wound healing. Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
Clinical aspects and prognosis of corneal burns mainly depend on the agent responsible for the trauma. The most severe burns are caustic burns, which should be classified as burns caused by basic agents, associated with deep and prolonged injuries, and burns caused by acidic agents, associated with more superficial injuries. At the acute stage, caustic burns induce epithelial defects, corneal edema, and ischemic necrosis of the limbus, conjunctiva, iris and ciliary body. At the early stage, reepithelialization occurs and is often associated with corneal vascularization and stromal infiltrates, followed by corneal scar formation. At the chronic stage, the following complications are possible: corneal scars, limbal stem cell insufficiency, lachrymal insufficiency, irregular astigmatism, ocular surface fibrosis, cataract, glaucoma, decreased intraocular pressure, and ocular atrophy. The Ropper-Hall classification is based on the extent of limbal ischemia. Thermal burns induce epithelial defects at the acute stage, with the more severe forms giving the same complications as caustic burns. Radiation-related burns can be caused by ultraviolet radiations (acute epithelial keratitis, pterygium, droplet-like keratitis), microwaves, infrared radiations, ionizing radiations or, laser radiations. Electrical burns are often a result of torture and give corneal stroma opacification.
Arba-Mosquera, Samuel; Merayo-Lloves, Jesús; de Ortueta, Diego
The calculation of corneal asphericity as a 3-D fit renders more accurate results when it is based on the corneal wavefront aberrations rather than on the corneal topography of the principal meridians. A more accurate prediction could be obtained for hyperopic treatments compared to myopic treatments. We evaluate a method to calculate corneal asphericity and asphericity changes after refractive surgery. Sixty eyes of 15 consecutive myopic patients and 15 consecutive hyperopic patients (n=30 each) are retrospectively evaluated. Preoperative and 3-month-postoperative topographic and corneal wavefront analyses are performed using corneal topography. Ablations are performed using a laser with an aberration-free profile. Topographic changes in asphericity and corneal aberrations are evaluated for a 6-mm corneal diameter. The induction of corneal spherical aberrations and asphericity changes correlates with the achieved defocus correction. Preoperatively as well as postoperatively, asphericity calculated from the topography meridians correlates with asphericity calculated from the corneal wavefront in myopic and hyperopic treatments. A stronger correlation between postoperative asphericity and the ideally expected/predicted asphericity is obtained based on aberration-free assumptions calculated from corneal wavefront values rather than from the meridians. In hyperopic treatments, a better correlation can be obtained compared to the correlation in myopic treatments. Corneal asphericity calculated from corneal wavefront aberrations represents a 3-D fit of the corneal surface; asphericity calculated from the main topographic meridians represents a 2-D fit of the principal corneal meridians. Postoperative corneal asphericity can be calculated from corneal wavefront aberrations with higher fidelity than from corneal topography of the principal meridians. Hyperopic treatments show a greater accuracy than myopic treatments.
Though conventional corneal transplantation has achieved great success, it still has several drawbacks including limited availability of donor corneas, recurrent allograft rejection, and subsequent graft failure in certain cases. Reconstructing clinically usable corneas by applying the technology of regenerative medicine can offer a solution to these problems, as well as making corneal transplantation a non-emergency surgery and enabling the usage of banked corneal cells. In the present study, we focused on corneal endothelium that is critical for corneal transparency and investigated the reconstruction of cornea utilizing cultured human corneal endothelial cells (HCECs). We succeeded in steadily culturing HCECs by using culture dishes pre-coated with extracellular matrix produced by calf corneal endothelial cells and culture media that contained basic fibroblast growth factor and fetal bovine serum. We performed the following analysis utilizing these cultured HCECs. The older the donor was, the more frequently large senescent cells appeared in the passaged HCECs. The telomeres of HCECs were measured as terminal restriction fragments (TRF) by Southern blotting. HCECs, in vivo from donors in their seventies had a long TRFs of over 12 kilobases. Passaging shortened the TRFs but there was no difference in TRFs among donors of various ages. These results indicated that shortening of telomere length is not related to senescence of HCECs. We investigated the role of advanced glycation end products (AGEs) in the senescence of in vivo HCECs. The results indicated that AGE-protein in the aqueous humor is endocytosed into HCECs via AGE receptors expressed on the surface of HCECs and damages HCECs by producing reactive oxygen species and inducing apoptosis, suggesting that AGEs, at least partly, cause the senescence of HECEs. HCECs were cultured using adult human serum instead of bovine serum to get rid of bovine material that can be infected with prions. Primary and passage
Swinger, C A; Kraushar, M F
Refractive corneal surgery (a collective term used to describe a variety of surgical procedures that alter the refractive status of the eye through the surgical modification of corneal curvature) shows promise for use in situations where current methods of optical correction do not meet the patient's needs. This article reviews our experiences with the retinal evaluation of patients who have undergone corneal refractive surgery and offers recommendations for the treatment of retinal pathology after such surgery.
Mashima, Y; Kawai, M; Yamada, M
Aims: To evaluate corneal electrolysis as a treatment for recurrent diffuse corneal opacities at the host-graft interface of the stroma or at the subepithelial region in two types of granular corneal dystrophy (GCD). Methods: Recurrence developed at the host-graft interface of the stroma after lamellar keratoplasty in a patient with Avellino corneal dystrophy (ACD). At surgery, the deep aspect of the graft in this patient was partially separated from host tissue to expose the deposits, with one third of the host-graft junction left intact. The graft was everted, and electrolysis was applied directly to remove the deposits attached to both surfaces of the host and the graft. Then the graft was returned to its place and sutured. In two patients with homozygous ACD and one patient with the superficial variant of GCD, diffuse subepithelial opacities developed following penetrating keratoplasty. Electrolysis was applied directly to the corneal surface. Results: Deposits at the host-graft interface of the stroma and in the subepithelial region disappeared following treatment, and vision recovered in all patients. Conclusions: This method is a simple, easy, and inexpensive way to remove deposits that recur after lamellar or penetrating keratoplasty. PMID:11864880
A unified mathematical model of two different modes of inception of fissures at the surface of articular cartilage in healthy and pathological joints. The superficial tangential zone of articular cartilage is modeled as a three-phase medium consisting of collagen fibers, matrix, and of infiltrated thin constituent of synovial fluid. The author's general mesomechanical concept is applied to the analysis of deterioration of articular cartilage. Theoretical analysis based on the results of the author's preceding paper. The presented analysis shows that superficial fissures in articular cartilage can also be caused by pathological thinning of synovial fluid. Whereas in healthy joints the probable cause of creation of fissures at the surface of cartilage was shown to be fast impact loading, in joints with inflammatory synovial fluid the fissures can be caused by plain walking. Appearance of surface fissures in articular cartilage is a serious, still not fully clarified problem that deserves attention.
Torquetti, Leonardo; Arce, Carlos; Merayo-Lloves, Jesús; Ferrara, Guilherme; Ferrara, Paulo; Signorelli, Brenno; Signorelli, Armando
AIM To evaluate corneal parameters measured with a dual Scheimpflug analyzer in keratoconus patients implanted with intrastromal corneal ring segments (ICRS). METHODS Fifty eyes of 40 keratoconus patients had Ferrara ICRS implantation from November 2010 to April 2014. Uncorrected visual acuity (UCVA), best corrected visual acuity (BCVA), refraction, keratometry, asphericity, elevation, pachymetry, root mean square (RMS), spherical aberration and coma were studied. All patients were evaluated using a dual Scheimpflug system. RESULTS The mean follow-up time after the procedure was 12.7mo. The mean UCVA improved from 0.82 to 0.31 (P<0.001); the mean BCVA improved from 0.42 to 0.05 (P<0.0001), the mean spherical refraction changed from -3.06±3.80 D to -0.80±2.5 D (P<0.0001) and the mean refraction astigmatism reduced from -4.51±2.08 D to -2.26±1.18 D (P<0.0001). The changes from preoperative to postoperative, in parameters of the anterior and posterior surface of the cornea, were statistically significant except the elevation posterior at the apex of the cornea and posterior asphericity. CONCLUSION The implantation of Ferrara ICRS induces changes in both anterior and posterior surfaces of the cornea. PMID:27672592
Trikha, Sameer; Sahu, Debendra; Jeffry, Margaret; Boase, David
We describe the case of a 37-year-old caucasian man with a history of keratoconus and long-term hard contact lens wear. Histological analysis of the corneal button after penetrating keratoplasty revealed staining with Congo red and apple green birefringence detected using polarized light. In the absence of other systemic or ocular pathology, the authors infer this amyloid deposition to be secondary to keratoconus and endeavor to discuss the possible etiopathogenesis of the disease.
Golubović, S; Parunović, A
The application of tissue adhesives to treat different corneal diseases has been used extensively in recent years. Owing to the widespread application, it has been possible to establish the advantages and disadvantages of this method of treatment. Keeping in mind the disadvantages (primarily the toxicity of cyanoacrylate glue for the corneal endothelium and lens when it comes into direct contact with these structures), the application of cyanoacrylate glue was restricted to the treatment of progressive corneal ulcerations where the risk of corneal perforation was recognized. This method of treatment was applied in 30 patients with corneal melting in dry eye associated with rheumatoid arthritis (12), trophic postherpetic ulcerations of the cornea (9), chemical corneal burns (7), neurotrophic corneal ulceration (1) and Mooren's ulcer (1). The defect healed and anterior corneal surface epithelization occurred in 73.33% of patients in contrast to the additional treatment, most commonly penetrating keratoplasty, required in the remaining patients (26.67%).
Mitsui, Iwane; Yamada, Yoshiya
To evaluate the corneal thickness and curvature changes after Orthokeratology contact lens wear, using the ORBSCAN II corneal topography system, corneal thickness and corneal curvature were measured on one hundred and twenty eyes of sixty patients before and after wearing the custom rigid gas permeable contact lenses for Orthokeratology. The contact lenses were specially designed for each eye. The subjects wore the orthokeratology lenses for approximately Four hours with their eyes closed. The corneal thickness of the subjects was increased on fifty-five eyes at not only the peripheral zone but also the center of the cornea. The average increase of central and peripheral corneal thickness was 18 micrometer and 22micrometer, respectively. The mean anterior curvature of corneal surface changed 1.25D. The mean posterior curvature of corneal endothelium side changed 0.75D.
Kurtz, Ron M.; Spooner, Greg J. R.; Sletten, Karin R.; Yen, Kimberly G.; Sayegh, Samir I.; Loesel, Frieder H.; Horvath, Christopher; Liu, HsiaoHua; Elner, Victor; Cabrera, Delia; Muenier, Marie-Helene; Sacks, Zachary S.; Juhasz, Tibor
We evaluated the efficacy, safety, and stability of femtosecond laser intrastromal refractive procedures in ex vivo and in vivo models. When compared with longer pulsewidth nanosecond or picosecond laser pulses, femtosecond laser-tissue interactions are characterized by significantly smaller and more deterministic photodisruptive energy thresholds, as well as reduced shock waves and smaller cavitation bubbles. We utilized a highly reliable, all-solid-state femtosecond laser system for all studies to demonstrate clinical practicality. Contiguous tissue effects were achieved by scanning a 5 μm focused laser spot below the corneal surface at pulse energies of approximately 2 - 4 microjoules. A variety of scanning patterns was used to perform three prototype procedures in animal eyes; corneal flap cutting, keratomileusis, and intrastromal vision correction. Superior dissection and surface quality results were obtained for lamellar procedures (corneal flap cutting and keratomileusis). Preliminary in vivo evaluation of intrastromal vision correction in a rabbit model revealed consistent and stable pachymetry changes, without significant inflammation or loss of corneal transparency. We conclude that femtosecond laser technology may be able to perform a variety of corneal refractive procedures with high precision, offering advantages over current mechanical and laser devices and techniques.
Della Vecchia, Michael A.; Lamkin-Kennard, Kathleen
Procedurally, excimer photorefractive keratectomy is based on the refractive correction of composite spherical and cylindrical ophthalmic errors of the entire eye. These refractive errors are inputted for correction at the corneal plane and for the properly controlled duration and location of laser energy. Topography is usually taken to correspondingly monitor spherical and cylindrical corneorefractive errors. While a corneal topographer provides surface morphologic information, the keratorefractive photoablation is based on the patient's spherical and cylindrical spectacle correction. Topography is at present not directly part of the procedural deterministic parameters. Examination of how corneal curvature at each of the keratometric reference loci affect the shape of the resultant corneal photoablated surface may enhance the accuracy of the desired correction. The objective of this study was to develop a methodology to utilize corneal topography for construction of models depicting pre- and post-operative keratomorphology for analysis of photorefractive keratectomy. Multiple types of models were developed then recreated in optical design software for examination of focal lengths and other optical characteristics. The corneal models were developed using data extracted from the TMS I corneal modeling system (Computed Anatomy, New York, NY). The TMS I does not allow for manipulation of data or differentiation of pre- and post-operative surfaces within its platform, thus models needed to be created for analysis. The data were imported into Matlab where 3D models, surface meshes, and contour plots were created. The data used to generate the models were pre- and post-operative curvatures, heights from the corneal apes, and x-y positions at 6400 locations on the corneal surface. Outlying non-contributory points were eliminated through statistical operations. Pre- and post- operative models were analyzed to obtain the resultant changes in the corneal surfaces during PRK
Executive Summary Objective The purpose of this project was to determine the role of corneal implants in the management of corneal thinning disease conditions. An evidence-based review was conducted to determine the safety, effectiveness and durability of corneal implants for the management of corneal thinning disorders. The evolving directions of research in this area were also reviewed. Subject of the Evidence-Based Analysis The primary treatment objectives for corneal implants are to normalize corneal surface topography, improve contact lens tolerability, and restore visual acuity in order to delay or defer the need for corneal transplant. Implant placement is a minimally invasive procedure that is purported to be safe and effective. The procedure is also claimed to be adjustable, reversible, and both eyes can be treated at the same time. Further, implants do not limit the performance of subsequent surgical approaches or interfere with corneal transplant. The evidence for these claims is the focus of this review. The specific research questions for the evidence review were as follows: Safety Corneal Surface Topographic Effects: Effects on corneal surface remodelling Impact of these changes on subsequent interventions, particularly corneal transplantation (penetrating keratoplasty [PKP]) Visual Acuity Refractive Outcomes Visual Quality (Symptoms): such as contrast vision or decreased visual symptoms (halos, fluctuating vision) Contact lens tolerance Functional visual rehabilitation and quality of life Patient satisfaction: Disease Process: Impact on corneal thinning process Effect on delaying or deferring the need for corneal transplantation Clinical Need: Target Population and Condition Corneal ectasia (thinning) comprises a range of disorders involving either primary disease conditions such as keratoconus and pellucid marginal corneal degeneration or secondary iatrogenic conditions such as corneal thinning occurring after LASIK refractive surgery. The condition
Twa, Michael D.; Vantipalli, Srilatha; Singh, Manmohan; Li, Jiasong; Larin, Kirill V.
Corneal biomechanical properties are influenced by several factors, including intraocular pressure, corneal thickness, and viscoelastic responses. Corneal thickness is directly proportional to tissue hydration and can influence corneal stiffness, but there is no consensus on the magnitude or direction of this effect. We evaluated the influence of corneal hydration on dynamic surface deformation responses using optical coherence elastography (OCE). Fresh rabbit eyes (n=10) were prepared by removing the corneal epithelium and dropping with 0.9% saline every 5 minutes for 1 hour, followed by 20% dextran solution every 5 minutes for one hour. Corneal thickness was determined from structural OCT imaging and OCE measurements were performed at baseline and every 20 minutes thereafter. Micron-scale deformations were induced at the apex of the corneal tissue using a spatially-focused (150μm) short-duration (<1ms) air-pulse delivery system. These dynamic tissue responses were measured non-invasively with a phase-stabilized swept source OCT system. The tissue surface deformation response (Relaxation Rate: RR) was quantified as the time constant, over which stimulated tissue recovered from the maximum deformation amplitude. Elastic wave group velocity (GV) was also quantified and correlated with change in corneal thickness due to hydration process. Corneal thickness rapidly increased and remained constant following epithelium removal and changed little thereafter. Likewise, corneal stiffness changed little over the first hour and then decreased sharply after Dextran application (thickness: -46% [-315/682 μm] RR: - 24% [-0.7/2.88 ms-1]; GV: -19% [-0.6/3.2 m/s]). Corneal thickness and corneal stiffness (RR) were well correlated (R2 = .66). Corneal biomechanical properties are highly correlated with tissue hydration over a wide range of corneal thickness and these changes in corneal stiffness are quantifiable using OCE.
Mah-Sadorra, Jeane Haidee; Najjar, Dany M; Rapuano, Christopher J; Laibson, Peter R; Cohen, Elisabeth J
To study the clinical and microbiological profile of Serratia corneal ulcers at the Cornea Service of the Wills Eye Hospital. This was a retrospective, observational case series. The clinical records of patients with Serratia marcescens corneal ulcers seen at the Cornea Service of the Wills Eye Hospital between January 1, 1998 and December 31, 2002 were reviewed. Twenty-four cases of Serratia keratitis were identified in 21 patients. Two patients (9.5%) had recurrent keratitis, 1 of which recurred twice. Both had corneal graft edema and were on topical steroids and antiglaucoma drops. The Serratia infection in 15 patients (71%) was associated with an abnormal corneal surface. Twelve of these patients (57%) had the ulcer in a corneal graft, 4 (19%) of which were associated with suture infiltrates. Fifteen patients (71%) were on topical medications-15 used corticosteroids and 13 used antiglaucoma drops. Six patients (29%) were contact lens wearers-1 had a concomitant suture infiltrate associated with a corneal graft, and 5 had otherwise healthy corneas. One isolate lacked in vitro susceptibility to ciprofloxacin and ofloxacin but was susceptible to gentamicin and tobramycin. Nineteen patients had a favorable response to medical therapy. Two patients with poor outcome had large corneal ulcers with severe necrosis and thinning associated with delay in treatment. Serratia marcescens keratitis is associated with the presence of an abnormal corneal surface, use of topical medications, and contact lens wear. Prompt medical therapy results in a good clinical response in the majority of cases.
Soiberman, Uri; Kambhampati, Siva P; Wu, Tony; Mishra, Manoj K; Oh, Yumin; Sharma, Rishi; Wang, Jiangxia; Al Towerki, Abdul Elah; Yiu, Samuel; Stark, Walter J; Kannan, Rangaramanujam M
Corneal inflammation is often encountered as a key pathological event in many corneal diseases. Current treatments involve topical corticosteroids which require frequent instillations due to rapid tear turnover, causing side-effects such as corneal toxicity and elevated intraocular pressure (IOP). Hence, new interventions that can reduce side effects, dosing frequency, and increase patient compliance can be highly beneficial. In this study, we explore a subconjunctival injectable gel based on G4-PAMAM dendrimer and hyaluronic acid, cross-linked using thiol-ene click chemistry, incorporated with dendrimer dexamethasone (D-Dex) conjugates as a potential strategy for sustained delivery and enhanced bioavailability of corticosteroids. The efficacy of the injectable gel formulation was evaluated in a rat mild alkali burn model. Fluorescently-labelled dendrimers (D-Cy5) incorporated in the gel release D-Cy5 in vivo. The released D-Cy5 selectively targets and localizes within corneal macrophages in inflamed rat cornea but not in healthy controls. This pathology dependent biodistribution was exploited for drug delivery, by incorporating D-Dex in the injectable gel. The attenuation of corneal inflammation by D-Dex gels was assessed using various clinical and biochemical parameters over a 2-week period. Subconjunctival D-Dex gel treatment resulted in favorable clinically-relevant outcomes with reduced central corneal thickness and improved corneal clarity compared to free-Dex and placebo gel controls. The extent of corneal neovascularization was significantly reduced in the D-Dex group. These findings suggest that D-Dex attenuates corneal inflammation more effectively than free-Dex by attenuating macrophage infiltration and pro-inflammatory cytokines expression. A significant elevation in IOP was not observed in the D-Dex group but was observed in the free-Dex group. This novel injectable D-Dex gel may be a potential drug delivery platform for the treatment of many
Secker, Genevieve A; Daniels, Julie T
The corneal epithelium is continuously renewed by a population of stem cells that reside in the corneoscleral junction, otherwise known as the limbus. These limbal epithelial stem cells (LESC) are imperative for corneal maintenance with deficiencies leading to in-growth of conjunctival cells, neovascularisation of the corneal stroma and eventual corneal opacity and visual loss. One such disease that has traditionally been thought to be due to LESC deficiency is aniridia, a pan-ocular congenital eye disease due to mutations in the PAX6 gene. Corneal changes or aniridia related keratopathy (ARK) seen in aniridia are typical of LESC deficiency. However, the pathophysiology behind ARK is still ill defined, with current theories suggesting it may be caused by a deficiency in the stem cell niche and adjacent corneal stroma, with altered wound healing responses also playing a role (Ramaesh et al, International Journal of Biochemistry & Cell Biology 37:547-557, 2005) or abnormal epidermal differentiation of LESC (Li et al., The Journal of Pathology 214:9, 2008). PAX6 is considered the master control gene for the eye and is required for normal eye development with expression continuing in the adult cornea, thus inferring a role for corneal repair and regeneration (Sivak et al., Developments in Biologicals 222:41-54, 2000). Studies of models of Pax6 deficiency, such as the small eyed (sey) mouse, should help to reveal the intrinsic and extrinsic mechanisms involved in normal LESC function.
Pajoohesh-Ganji, Ahdeah; Pal-Ghosh, Sonali; Tadvalkar, Gauri; Stepp, Mary Ann
Goblet cells are terminally differentiated cells secreting mucins and anti-bacterial peptides that play an important role in maintaining the health of the cornea. In corneal stem cell deficiency, the progenitor cells giving rise to goblet cells on the cornea are presumed to arise from differentiation of cells that migrate onto the cornea from the neighboring conjunctiva. This occurs in response to the inability of corneal epithelial progenitor cells at the limbus to maintain an intact corneal epithelium. This study characterizes clusters of cells we refer to as compound niches at the limbal:corneal border in the unwounded mouse. Compound niches are identified by high expression of simple epithelial keratin 8 (K8) and 19 (K19). They contain variable numbers of cells in one of several differentiation states: slow-cycling corneal progenitor cells, proliferating cells, non-proliferating cells, and post-mitotic differentiated K12+Muc5ac+goblet cells. Expression of K12 differentiates these goblet cells from those in the conjunctival epithelium and suggests that corneal epithelial progenitor cells give rise to both corneal epithelial and goblet cells. After wounds that remove corneal epithelial cells near the limbus, compound niches migrate from the limbal:corneal border onto the cornea where K8+ cells proliferate and goblet cells increase in number. By contrast, no migration of goblet cells from the bulbar conjunctiva onto the cornea is observed. This study is the first description of compound niches and corneal goblet cells and demonstration of a role for these cells in the pathology typically associated with corneal stem cell deficiency. PMID:22821715
Williams, Lynn B; Pinard, Chantale L
Corneal ulceration is commonly diagnosed by equine veterinarians. A complete ophthalmic examination as well as fluorescein staining, corneal cytology, and corneal bacterial (aerobic) and fungal culture and sensitivity testing are necessary for all infected corneal ulcers. Appropriate topical antibiotics, topical atropine, and systemic NSAIDs are indicated for all corneal ulcers. If keratomalacia (melting) is observed, anticollagenase/antiprotease therapy, such as autologous serum, is indicated. If fungal infection is suspected, antifungal therapy is a necessity. Subpalpebral lavage systems allow convenient, frequent, and potentially long-term therapy. Referral corneal surgeries provide additional therapeutic options when the globe's integrity is threatened or when improvement has not been detected after appropriate therapy.
Woodward, Maria A.; Titus, Michael; Mavin, Kyle; Shtein, Roni M.
Over the past ten years, corneal transplantation surgical techniques have undergone revolutionary changes1,2. Since its inception, traditional full thickness corneal transplantation has been the treatment to restore sight in those limited by corneal disease. Some disadvantages to this approach include a high degree of post-operative astigmatism, lack of predictable refractive outcome, and disturbance to the ocular surface. The development of Descemet's stripping endothelial keratoplasty (DSEK), transplanting only the posterior corneal stroma, Descemet's membrane, and endothelium, has dramatically changed treatment of corneal endothelial disease. DSEK is performed through a smaller incision; this technique avoids 'open sky' surgery with its risk of hemorrhage or expulsion, decreases the incidence of postoperative wound dehiscence, reduces unpredictable refractive outcomes, and may decrease the rate of transplant rejection3-6. Initially, cornea donor posterior lamellar dissection for DSEK was performed manually1 resulting in variable graft thickness and damage to the delicate corneal endothelial tissue during tissue processing. Automated lamellar dissection (Descemet's stripping automated endothelial keratoplasty, DSAEK) was developed to address these issues. Automated dissection utilizes the same technology as LASIK corneal flap creation with a mechanical microkeratome blade that helps to create uniform and thin tissue grafts for DSAEK surgery with minimal corneal endothelial cell loss in tissue processing. Eye banks have been providing full thickness corneas for surgical transplantation for many years. In 2006, eye banks began to develop methodologies for supplying precut corneal tissue for endothelial keratoplasty. With the input of corneal surgeons, eye banks have developed thorough protocols to safely and effectively prepare posterior lamellar tissue for DSAEK surgery. This can be performed preoperatively at the eye bank. Research shows no significant difference
García, Beatriz; Merayo-Lloves, Jesús; Rodríguez, David; Alcalde, Ignacio; García-Suárez, Olivia; Alfonso, José F.; Baamonde, Begoña; Fernández-Vega, Andrés; Vazquez, Fernando; Quirós, Luis M.
The epithelium of the cornea is continuously exposed to pathogens, and adhesion to epithelial cells is regarded as an essential first step in bacterial pathogenesis. In this article, the involvement of glycosaminoglycans in the adhesion of various pathogenic bacteria to corneal epithelial cells is analyzed. All microorganisms use glycosaminoglycans as receptors, but arranged in different patterns depending on the Gram-type of the bacterium. The heparan sulfate chains of syndecans are the main receptors, though other molecular species also seem to be involved, particularly in Gram-negative bacteria. Adherence is inhibited differentially by peptides, including heparin binding sequences, indicating the participation of various groups of Gram-positive, and -negative adhesins. The length of the saccharides produces a major effect, and low molecular weight chains inhibit the binding of Gram-negative microorganisms but increase the adherence of Gram-positives. Pathogen adhesion appears to occur preferentially through sulfated domains, and is very dependent on N- and 6-O-sulfation of the glucosamine residue and, to a lesser extent, 2-O sulfation of uronic acid. These data show the differential use of corneal receptors, which could facilitate the development of new anti-infective strategies. PMID:27965938
García, Beatriz; Merayo-Lloves, Jesús; Rodríguez, David; Alcalde, Ignacio; García-Suárez, Olivia; Alfonso, José F; Baamonde, Begoña; Fernández-Vega, Andrés; Vazquez, Fernando; Quirós, Luis M
The epithelium of the cornea is continuously exposed to pathogens, and adhesion to epithelial cells is regarded as an essential first step in bacterial pathogenesis. In this article, the involvement of glycosaminoglycans in the adhesion of various pathogenic bacteria to corneal epithelial cells is analyzed. All microorganisms use glycosaminoglycans as receptors, but arranged in different patterns depending on the Gram-type of the bacterium. The heparan sulfate chains of syndecans are the main receptors, though other molecular species also seem to be involved, particularly in Gram-negative bacteria. Adherence is inhibited differentially by peptides, including heparin binding sequences, indicating the participation of various groups of Gram-positive, and -negative adhesins. The length of the saccharides produces a major effect, and low molecular weight chains inhibit the binding of Gram-negative microorganisms but increase the adherence of Gram-positives. Pathogen adhesion appears to occur preferentially through sulfated domains, and is very dependent on N- and 6-O-sulfation of the glucosamine residue and, to a lesser extent, 2-O sulfation of uronic acid. These data show the differential use of corneal receptors, which could facilitate the development of new anti-infective strategies.
Brodie, S E
A simple trigonometric analysis of the Hirschberg test with the assumption that the corneal surface is spherical predicts a sinusoidal dependence of the corneal reflex displacement on the angle of ocular rotation. A comparison with corneal reflex photographs demonstrates that at angles larger than 50 prism diopters (26 deg) the reflex displacements are larger than predicted by the spherical model. This discrepancy may be accounted for by incorporating a more general description of the corneal topography into the geometric analysis. The linear Hirschberg relation that is seen in typical data is accounted for by a relative flattening of the peripheral cornea by ~ 20% of the apical curvature. This geometric analysis of the functional dependence of the Hirschberg relation on the corneal topography can be expressed as an integral equation. Differentiation yields a second-order differential equation for the corneal topography in terms of the Hirschberg data. If the Hirschberg relation is assumed to be linear, a quadratic dependence is found for the corneal curvature. A similar differential approach can be formulated for the Placido disk. In this sense the corneal topography problem given in terms of Placido disk data is shown to be wellformulated. The relative simplicity of the Hirschberg geometry is seen to stem from the alignment of the light source with the eye of the observer.
García, Beatriz; García-Suárez, Olivia; Merayo-Lloves, Jesús; Alcalde, Ignacio; Alfonso, José F; Fernández-Vega Cueto, Luis; Meana, Álvaro; Vázquez, Fernando; Quirós, Luis M
Keratoconus is a heterogeneous disease associated with a range of pathologies, including disorders that involve proteoglycans (PGs). Some PG alterations, mainly in keratan sulfate (KS), occur in keratoconus. In this article, we studied the differential expression of the genes encoding PGs in cells isolated from keratoconus patients and healthy controls, as well as in corneal sections. Human central corneal tissue was obtained from cadaver donors and patients undergoing penetrating keratoplasty surgery. A transcriptomic approach was used, employing quantitative PCR, to analyze both the expression of the enzymes involved in glycosaminoglycan (GAG) biosynthesis and the PG core proteins. The expressions of the differentially expressed core proteins and of the GAG chains were also analyzed by immunocytochemistry in the cultured cells, as well as by immunohistochemistry in corneal sections. The mRNA levels of most major matrix PG mRNAs in the cultured keratoconic stromal cells decreased except collagen XVIII, which increased. At keratocyte surfaces, some heparan sulfate PGs were down-regulated. With respect to GAGs, there were changes in gene expression for the polymerization of the GAG chains, mainly KS and chondroitin sulfate, and in the modification of the saccharidic chains, pointing to an alteration of the sulfation patterns of all GAG species. Most of the PG core proteins underwent significant changes in cultured keratoconic cells and corneas. With regard to GAG chains, the polymerization of the chains and their chemical modification was modified in way that depended on the specific type of GAG involved.
Talbot, Christopher; Jordan, Thomas M; Roberts, Nicholas W; Collin, Shaun P; Marshall, N Justin; Temple, Shelby E
The cornea is the first optical element in the path of light entering the eye, playing a role in image formation and protection. Corneas of vertebrate simple camera-type eyes possess microprojections on the outer surface in the form of microridges, microvilli, and microplicae. Corneas of invertebrates, which have simple or compound eyes, or both, may be featureless or may possess microprojections in the form of nipples. It was previously unknown whether cephalopods (invertebrates with camera-type eyes like vertebrates) possess corneal microprojections and, if so, of what form. Using scanning electron microscopy, we examined corneas of a range of cephalopods and discovered nipple-like microprojections in all species. In some species, nipples were like those described on arthropod compound eyes, with a regular hexagonal arrangement and sizes ranging from 75 to 103 nm in diameter. In others, nipples were nodule shaped and irregularly distributed. Although terrestrial invertebrate nipples create an antireflective surface that may play a role in camouflage, no such optical function can be assigned to cephalopod nipples due to refractive index similarities of corneas and water. Their function may be to increase surface-area-to-volume ratio of corneal epithelial cells to increase nutrient, gas, and metabolite exchange, and/or stabilize the corneal mucous layer, as proposed for corneal microprojections of vertebrates.
Jing, Qinghe; Tang, Yating; Qian, Dongjin; Lu, Yi; Jiang, Yongxiang
Purpose To evaluate the characteristics of the posterior corneal surface in patients with high myopia before cataract surgery. Methods We performed a cross-sectional study at the Eye and ENT Hospital of Fudan University, Shanghai, China. Corneal astigmatism and axial length were measured with a rotating Scheimpflug camera (Pentacam) and partial coherence interferometry (IOLMaster) in a high-myopia study group of 167 eyes (axial length ≥ 26 mm) and a control group of 150 eyes (axial length > 20 mm and < 25 mm). Results Total corneal astigmatism and anterior corneal astigmatism values were higher in the high-myopia group than in the control group. There was no significant difference in posterior corneal astigmatism between the high-myopia study group and the control group. In the study group, the mean posterior corneal astigmatism (range 0 – −0.9 diopters) was –0.29 diopters (D) ± 0.17 standard deviations (SD). The steep corneal meridian was aligned vertically (60°–120°) in 87.43% of eyes for the posterior corneal surface, and did not change with increasing age. There was a significant correlation (r = 0.235, p = 0.002) between posterior corneal astigmatism and anterior corneal astigmatism, especially when the anterior corneal surface showed with-the-rule (WTR) astigmatism (r = 0.452, p = 0.000). There was a weak negative correlation between posterior corneal astigmatism and age (r = –0.15, p = 0.053) in the high-myopia group. Compared with total corneal astigmatism values, the anterior corneal measurements alone overestimated WTR astigmatism by a mean of 0.27 ± 0.18 D in 68.75% of eyes, underestimated against-the-rule (ATR) astigmatism by a mean of 0.41 ± 0.28 D in 88.89% of eyes, and underestimated oblique astigmatism by a mean of 0.24 ± 0.13 D in 63.64% of eyes. Conclusions Posterior corneal astigmatism decreased with age and remained as ATR astigmatism in most cases of high myopia. There was a significant correlation between posterior corneal
Jing, Qinghe; Tang, Yating; Qian, Dongjin; Lu, Yi; Jiang, Yongxiang
To evaluate the characteristics of the posterior corneal surface in patients with high myopia before cataract surgery. We performed a cross-sectional study at the Eye and ENT Hospital of Fudan University, Shanghai, China. Corneal astigmatism and axial length were measured with a rotating Scheimpflug camera (Pentacam) and partial coherence interferometry (IOLMaster) in a high-myopia study group of 167 eyes (axial length ≥ 26 mm) and a control group of 150 eyes (axial length > 20 mm and < 25 mm). Total corneal astigmatism and anterior corneal astigmatism values were higher in the high-myopia group than in the control group. There was no significant difference in posterior corneal astigmatism between the high-myopia study group and the control group. In the study group, the mean posterior corneal astigmatism (range 0 - -0.9 diopters) was -0.29 diopters (D) ± 0.17 standard deviations (SD). The steep corneal meridian was aligned vertically (60°-120°) in 87.43% of eyes for the posterior corneal surface, and did not change with increasing age. There was a significant correlation (r = 0.235, p = 0.002) between posterior corneal astigmatism and anterior corneal astigmatism, especially when the anterior corneal surface showed with-the-rule (WTR) astigmatism (r = 0.452, p = 0.000). There was a weak negative correlation between posterior corneal astigmatism and age (r = -0.15, p = 0.053) in the high-myopia group. Compared with total corneal astigmatism values, the anterior corneal measurements alone overestimated WTR astigmatism by a mean of 0.27 ± 0.18 D in 68.75% of eyes, underestimated against-the-rule (ATR) astigmatism by a mean of 0.41 ± 0.28 D in 88.89% of eyes, and underestimated oblique astigmatism by a mean of 0.24 ± 0.13 D in 63.64% of eyes. Posterior corneal astigmatism decreased with age and remained as ATR astigmatism in most cases of high myopia. There was a significant correlation between posterior corneal astigmatism and anterior corneal astigmatism
Miyake, Toshiyuki; Shimizu, Kimiya; Kamiya, Kazutaka
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. PMID:25625283
Miyake, Toshiyuki; Shimizu, Kimiya; Kamiya, Kazutaka
To investigate the distribution of posterior corneal astigmatism in eyes with with-the-rule (WTR) and against-the-rule (ATR) anterior corneal astigmatism. 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. 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. 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.
Kryuchkov, Michail; Katanaev, Vladimir L; Enin, Gennadiy A; Sergeev, Anton; Timchenko, Alexander A; Serdyuk, Igor N
Drosophila melanogaster is a model organism instrumental for numerous biological studies. The compound eye of this insect consists of some eight hundred individual ommatidia or facets, ca. 15 µm in cross-section. Each ommatidium contains eighteen cells including four cone cells secreting the lens material (cornea). High-resolution imaging of the cornea of different insects has demonstrated that each lens is covered by the nipple arrays--small outgrowths of ca. 200 nm in diameter. Here we for the first time utilize atomic force microscopy (AFM) to investigate nipple arrays of the Drosophila lens, achieving an unprecedented visualization of the architecture of these nanostructures. We find by Fourier analysis that the nipple arrays of Drosophila are disordered, and that the seemingly ordered appearance is a consequence of dense packing of the nipples. In contrast, Fourier analysis confirms the visibly ordered nature of the eye microstructures--the individual lenses. This is different in the frizzled mutants of Drosophila, where both Fourier analysis and optical imaging detect disorder in lens packing. AFM reveals intercalations of the lens material between individual lenses in frizzled mutants, providing explanation for this disorder. In contrast, nanostructures of the mutant lens show the same organization as in wild-type flies. Thus, frizzled mutants display abnormal organization of the corneal micro-, but not nano-structures. At the same time, nipples of the mutant flies are shorter than those of the wild-type. We also analyze corneal surface of glossy-appearing eyes overexpressing Wingless--the lipoprotein ligand of Frizzled receptors, and find the catastrophic aberration in nipple arrays, providing experimental evidence in favor of the major anti-reflective function of these insect eye nanostructures. The combination of the easily tractable genetic model organism and robust AFM analysis represents a novel methodology to analyze development and architecture of
Corneal cross-linking is nowadays the most used strategy for the treatment of keratoconus and recently it has been exploited for an increasing number of different corneal pathologies, from other ectatic disorders to keratitis. The safety of this technique has been widely assessed, but clinical complications still occur. The potential effects of cross-linking treatment upon the limbus are incompletely understood; it is important therefore to investigate the effect of UV exposure upon the limbal niche, particularly as UV is known to be mutagenic to cellular DNA and the limbus is where ocular surface tumors can develop. The risk of early induction of ocular surface cancer is undoubtedly rare and has to date not been published other than in one case after cross-linking. Nevertheless it is important to further assess, understand, and reduce where possible any potential risk. The aim of this review is to summarize all the reported cases of a pathological consequence for the limbal cells, possibly induced by cross-linking UV exposure, the studies done in vitro or ex vivo, the theoretical bases for the risks due to UV exposure, and which aspects of the clinical treatment may produce higher risk, along with what possible mechanisms could be utilized to protect the limbus and the delicate stem cells present within it. PMID:27689081
Smith, D G; Roberge, R J
Bee stings of the cornea are rarely reported, but have the potential for causing serious ophthalmologic injuries. We present a case of corneal bee sting with retained stinger apparatus and associated iritis and discuss the pathologic mechanisms of injury, evaluation, and treatment of these uncommon presentations.
Romero-Díaz de León, Lorena; Morales-León, Jorge-Emmanuel; Ledesma-Gil, Jasbeth; Navas, Alejandro
The purpose of the study is to measure corneal and conjunctival sensitivity in patients under glaucoma topical treatment as compared to a control group. It is a case-control study. Corneal and conjunctival esthesiometry were carried out through a Cochet-Bonnet esthesiometer. We took healthy individuals as controls, who did not use any type of ophthalmic topical medications and without history of ocular surface pathology or irritation. The study group was subdivided per number of applications (1, 2, and 3 or more applications). From a total 182 eyes from 91 patients, of which 26 (28.57 %) were controls and 65 (71.43 %) were in the study group, a mean corneal sensitivity of 58.98 ± 2.25 mm was found in the control group and 52.97 ± 6.41 mm in patients using topical medication. Mean conjunctival sensitivity was 18.80 ± 5.40 mm in the control group and 11.76 ± 5.45 mm in the study group. There was no statistically significant difference among groups when separated by 1, 2, and 3 or more applications. Eyes under use of timolol-containing medications showed lower sensitivity values as compared to other topical antiglaucoma medications. Corneal and conjunctival sensitivities are diminished in patients with chronic use of topical hypotensive medications and these results can explain the lack of correlation between signs and symptoms that is typically found in patients treated for glaucoma or ocular hypertension.
Tatini, Francesca; Rossi, Francesca; Coppi, Elisabetta; Magni, Giada; Fusco, Irene; Menabuoni, Luca; Pedata, Felicita; Pugliese, Anna Maria; Pini, Roberto
The characterization of the ion channels in corneal endothelial cells and the elucidation of their involvement in corneal pathologies would lead to the identification of new molecular target for pharmacological treatments and to the clarification of corneal physiology. The corneal endothelium is an amitotic cell monolayer with a major role in preserving corneal transparency and in regulating the water and solute flux across the posterior surface of the cornea. Although endothelial cells are non-excitable, they express a range of ion channels, such as voltage-dependent Na+ channels and K+ channels, L-type Ca2 channels and many others. Interestingly, purinergic receptors have been linked to a variety of conditions within the eye but their presence in the endothelium and their role in its pathophysiology is still uncertain. In this study, we were able to extract endothelial cells from single human corneas, thus obtaining primary cultures that represent the peculiarity of each donor. Corneas were from tissues not suitable for transplant in patients. We characterized the endothelial cells by confocal microscopy, both within the intact cornea and in the primary endothelial cells cultures. We also studied the functional role of the purinergic system (adenosine, ATP and their receptors) by means of electrophysiological recordings. The experiments were performed by patch clamp recordings and confocal time-lapse microscopy and our results indicate that the application of purinergic compounds modulates the amplitude of outward currents in the isolated endothelial cells. These findings may lead to the proposal of new therapies for endothelium-related corneal diseases.
Kumar, Vijay; Kumar, Asha
Corneal transplant is the most common solid tissue transplant in humans. Advances in microsurgical techniques, eye banking and the use of corticosteroids have improved the success of corneal transplants. Over 65,000 corneal transplants are being performed worldwide annually. Most of these transplants are performed in developed countries. Cornea is considered an immune privileged site. Despite this, immune mediated graft rejection is the most single cause of cornea graft failure and is one of the major postoperative complications. Incidences from as low as 2% to as high as 50% have been reported depending upon the degree of vascularization. Rejection involves donor tissue recognition and various factors may influence this rejection. Major factors include the antigenic load of the donor tissue; other factors include death to enucleation time, methods and temperature of preserving the tissue. Host factors that may impact the graft include ocular surface diseases such as dry eye, chemical burns and autoimmune diseases such as mucous membrane pemphigoid. Following infection, surgery or trauma, cells of the innate immune system invade the cornea as a result of up-regulation of cytokines, cellular adhesion molecules and growth and angiogenic factors. These factors results in neoangiogenesis and lymphoangiogenesis, leading to immune activation and graft rejection. The various immunological mechanisms that may play a role in the corneal transplant are discussed.
Furlan, Walter D; García-Delpech, Salvador; Udaondo, Patricia; Remón, Laura; Ferrando, Vicente; Monsoriu, Juan A
A conceptually new type of corneal inlays for a customized treatment of presbyopia is presented. The diffractive inlay consists on a small aperture disc having an array of micro-holes distributed inside the open zones of a Fresnel zone plate. In this way, the central hole of the disc lets pass the zero order diffraction and produces an extension of the depth of far focus of the eye, while the diffracted light through the holes in the periphery produce the near focus. Additionally, the micro-holes in the inlay surface fulfill the essential requirement of allowing the flow of nutrients through it to the cells of the corneal stroma. Theoretical and optical-bench experimental results for the polychromatic axial Point Spread Function (PSF) were obtained, showing an improved performance compared to the small aperture corneal inlay currently in the market (Kamra). Images of a test object, obtained at several vergences in the surroundings of the far and near foci, are also shown. Picture: Simulation of the appearance of the Diffractive corneal inlay on a real eye. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
Liliensiek, S J; Campbell, S; Nealey, P F; Murphy, C J
The cornea is a complex tissue composed of different cell types, including corneal epithelial cells and keratocytes. Each of these cell types are directly exposed to rich nanoscale topography from the basement membrane or surrounding extracellular matrix. Nanoscale topography has been shown to influence cell behaviors, including orientation, alignment, differentiation, migration, and proliferation. We investigated whether proliferation of SV40-transformed human corneal epithelial cells (SV40-HCECs), primary human corneal epithelial cells (HCECs), and primary corneal fibroblasts is influenced by the scale of topographic features of the substratum. Using basement membrane feature sizes as our guide and the known dimensions of collagen fibrils of the corneal stroma (20-60 nm), we fabricated polyurethane molded substrates, which contain anisotropic feature sizes ranging from 200-2000 nm on pitches ranging from 400 to 4000 nm (pitch = ridge width + groove width). The planar regions separating each of the six patterned regions served as control surfaces. Primary corneal and SV40-HCEC proliferation decreased in direct response to decreasing nanoscale topographies down to 200 nm. In contrast to corneal epithelial cells, corneal fibroblasts did not exhibit significantly different response to any of the topographies when compared with planar controls at 5 days. However, decreased proliferation was observed on the smallest feature sizes after 14 days in culture. Results from these experiments are relevant in understanding the potential mechanisms involved in the control of proliferation and differentiation of cells within the cornea.
Lambiase, Alessandro; Sacchetti, Marta; Mastropasqua, Alessandra; Bonini, Stefano
Neurotrophic keratitis (NK) represents a sight-threatening complication after trigeminal impairment. To our knowledge, the duration for which trigeminal injury may affect corneal structures and function has not been investigated previously. To describe the long-term clinical, morphological, and functional outcomes of NK after neurosurgical trigeminal damage. Observational case series performed at a corneal and ocular surface diseases referral center in 2010. Eight consecutive patients with monolateral NK from 1 to 19 years after neurosurgery and 20 age- and sex-matched healthy participants were included. Complete eye examination, tear film function tests, corneal staining, and Cochet-Bonnet esthesiometry were performed. The number and density of corneal nerves, number of hyperreflective keratocytes, and corneal epithelial, endothelial, and keratocyte cell densities were evaluated by in vivo slit scanning confocal microscopy. Clinical and morphological data were compared with the contralateral unaffected eyes and with the eyes of healthy control participants. All patients showed superficial punctate keratitis and dry eye in the NK eye and a healthy contralateral eye. Decreased corneal sensitivity was observed in all affected eyes (mean [SD], 2.0 [1.9] mm in the affected eyes vs 5.8 [0.3] mm in the contralateral unaffected eyes; P = .01) and was related to decreased subbasal nerve length (P = .04; R = 0.895). Corneal epithelial and endothelial cell densities were significantly decreased and the number of hyperreflective keratocytes was significantly increased in NK eyes compared with contralateral unaffected eyes and with the eyes of healthy participants. A longer duration of NK was associated with lower endothelial cell density (P = .046; R = -0.715). Corneal morphology and function were impaired even years after neurosurgical trigeminal damage, suggesting that assessment of tear film and corneal sensitivity as well as in vivo confocal microscopy examination should
Lopes, Bernardo T; Ramos, Isaac C; Dawson, Daniel G; Belin, Michael W; Ambrósio, Renato
Pentacam is a rotating Scheimpflug-based corneal and anterior segment tomographer that gives as comprehensive analysis of corneal 3D geometry. With this device the detection of mild keratoconus or ectasia susceptibility is possible. This is fundamental for screening ectasia risk prior to laser vision correction. The identification of susceptible cases at risk for developing progressive iatrogenic ectasia should go beyond (but not over) corneal front surface topography.
Baran, Inna; Bradley, James A; Alipour, Fateme; Rosenthal, Perry; Le, Hong-Gam; Jacobs, Deborah S
Prosthetic replacement of the ocular surface ecosystem (PROSE) uses custom designed and fabricated prosthetic devices in a treatment that restores vision, supports healing, reduces symptoms and improves quality of life in patients with complex corneal disease. We report the success rate for PROSE treatment of corneal ectasia. Records of 59 patients with corneal ectasia seen in consultation over 6 months were reviewed. Candidacy for treatment, topographic indices, change in visual acuity, achievement of satisfactory fit, device wear status and change in visual function at 6 months were recorded. Sixteen eyes were non-candidates because conventional correction was adequate. Trial devices were inserted but not dispensed for 13 eyes. No eyes were excluded for severity of ectasia. In the remaining 89 eyes, satisfactory fit was achieved and a device was dispensed. Twenty-one eyes (15 patients) had undergone penetrating keratoplasty. Device wear at 6 months was documented in 78/89 eyes (88%). NEI VFQ-25 score improved 27.6 points (p<0.001) on a 100 point scale in patients wearing a device at 6 months. All candidate eyes with corneal ectasia could be fitted with a PROSE device. PROSE treatment has a high success rate when measured by ability to achieve satisfactory fit, impact on visual acuity and 6 month data on both rate of continued wear and impact on visual function. PROSE treatment is an alternative to penetrating keratoplasty for patients with corneal ectasia who are contact lens intolerant. Copyright © 2012 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.
Hsu, Chih-Chien; Peng, Chi-Hsien; Hung, Kuo-Hsuan; Lee, Yi-Yen; Lin, Tai-Chi; Jang, Shih-Fan; Liu, Jorn-Hon; Chen, Yan-Ting; Woung, Lin-Chung; Wang, Chien-Ying; Tsa, Ching-Yao; Chiou, Shih-Hwa; Chen, Shih-Jen; Chang, Yuh-Lih
The ocular surface is the outermost part of the visual system that faces many extrinsic or intrinsic threats, such as chemical burn, infectious pathogens, thermal injury, Stevens-Johnson syndrome, ocular pemphegoid, and other autoimmune diseases. The cornea plays an important role in conducting light into the eyes and protecting intraocular structures. Several ocular surface diseases will lead to the neovascularization or conjunctivalization of corneal epithelium, leaving opacified optical media. It is believed that some corneal limbal cells may present stem cell-like properties and are capable of regenerating corneal epithelium. Therefore, cultivation of limbal cells and reconstruction of the ocular surface with these limbal cell grafts have attracted tremendous interest in the past few years. Currently, stem cells are found to potentiate regenerative medicine by their capability of differentiation into multiple lineage cells. Among these, the most common cell sources for clinical use are embryonic, adult, and induced stem cells. Different stem cells have varied specific advantages and limitations for in vivo and in vitro expansion. Other than ocular surface diseases, culture and transplantation of corneal endothelial cells is another major issue for corneal decompensation and awaits further studies to find out comprehensive solutions dealing with nonregenerative corneal endothelium. Recently, studies of in vitro endothelium culture and ρ-associated kinase (ROCK) inhibitor have gained encouraging results. Some clinical trials have already been finished and achieved remarkable vision recovery. Finally, nanotechnology has shown great improvement in ocular drug delivery systems during the past two decades. Strategies to reconstruct the ocular surface could combine with nanoparticles to facilitate wound healing, drug delivery, and even neovascularization inhibition. In this review article, we summarized the major advances of corneal limbal stem cells, limbal stem
Hegarty, Deborah M; Hermes, Sam M; Yang, Katherine; Aicher, Sue A
The surface of the cornea contains the highest density of nociceptive nerves of any tissue in the body. These nerves are responsive to a variety of modalities of noxious stimuli and can signal pain even when activated by low threshold stimulation. Injury of corneal nerves can lead to altered nerve morphology, including neuropathic changes which can be associated with chronic pain. Emerging technologies that allow imaging of corneal nerves in vivo are spawning questions regarding the relationship between corneal nerve density, morphology, and function. We tested whether noxious stimulation of the corneal surface can alter nerve morphology and neurochemistry. We used concentrations of menthol, capsaicin, and hypertonic saline that evoked comparable levels of nocifensive eye wipe behaviors when applied to the ocular surface of an awake rat. Animals were sacrificed and corneal nerves were examined using immunocytochemistry and three-dimensional volumetric analyses. We found that menthol and capsaicin both caused a significant reduction in corneal nerve density as detected with β-tubulin immunoreactivity 2 hr after stimulation. Hypertonic saline did not reduce nerve density, but did cause qualitative changes in nerves including enlarged varicosities that were also seen following capsaicin and menthol stimulation. All three types of noxious stimuli caused a depletion of CGRP from corneal nerves, indicating that all modalities of noxious stimuli evoked peptide release. Our findings suggest that studies aimed at understanding the relationship between corneal nerve morphology and chronic disease may also need to consider the effects of acute stimulation on corneal nerve morphology.
Ding, Juan; Wirostko, Barbara; Sullivan, David A
Purpose Corneal wound healing is a highly regulated process that requires the proliferation and migration of epithelial cells and interactions between epithelial cells and stromal fibroblasts. Compounds that can be applied topically to the ocular surface and that have the capability of activating corneal epithelial cells to proliferate and/or migrate would be useful to promote corneal wound healing. We hypothesize that human growth hormone (HGH) will activate Signal Transducer and Activators of Transcription-5 (STAT5) signaling and promote corneal wound healing by enhancing corneal epithelial cell and fibroblast proliferation and/or migration in vitro. The purpose of this study is to test these hypotheses. Methods We studied cell signaling, proliferation and migration using an immortalized human corneal epithelial cell line and primary human corneal fibroblasts in vitro. We also examined whether insulin-like growth factor-1 (IGF-1), a hormone known to mediate many of HGH’s growth promoting actions, may play a role in this effect. Results We show that HGH activates STAT5 signaling and promotes corneal epithelial cell migration in vitro. The migratory effect requires an intact communication between corneal epithelia and fibroblasts, and is not mediated by IGF-1. Conclusion HGH may represent a topical therapeutic to promote corneal epithelial wound healing. This warrants further investigation. PMID:25782399
Bakker, Ann-Christin; Langer, Barbara
Pathological changes and disorders of the cornea are a major cause of severe visual impairment and blindness. Replacement of a pathologically altered cornea with healthy corneal tissue from the eye of a suitable donor is among the most common and successful transplantation procedures in medicine. In Germany, approximately 5000-6000 corneal transplantations are performed each year, but the total demand per year is estimated to be twice as high. With a success rate of 90%, the outcome of cornea transplantation is very favourable. However, long-term maintenance and regeneration of a healthy new cornea requires tissue-specific corneal stem cells residing at the basal layer of the limbus, which is the annular transition zone between the cornea and sclera. When this important limbal stem cell population is destroyed or dysfunctional, a pathological condition known as limbal stem cell deficiency (LSCD) manifests. Limbal stem cell deficiency describes conditions associated with impaired corneal wound healing and regeneration. In this situation, transplantation of healthy limbal stem cells is the only curative treatment approach for restoration of an intact and functional ocular surface. To date, treatment of LSCD presents a great challenge for ophthalmologists. However, innovative, cell-therapeutic approaches may open new, promising treatment perspectives. In February 2015, the European Commission granted marketing authorization to the first stem cell-based treatment in the European Union. The product named Holoclar® is an advanced therapy medicinal product (ATMP) for the treatment of moderate to severe LSCD due to physical and chemical burns in adults. Further cell-based treatment approaches are in clinical development.
Tanhehco, Tasha Y; Chiavetta, Stephen V; Lee, Paul P; Fowler, Amy M; Afshari, Natalie A
The authors describe an extreme case of ciprofloxacin deposition on the corneal graft of a 67-year-old man with a history of penetrating keratoplasty for corneal ulcer and perforation, who presented with dense, gray deposits on the anterior corneal surface after being treated with ciprofloxacin for an epithelial defect. The deposits resolved after ciprofloxacin was discontinued. The non-physiologic pH of the drug formulation is thought to trigger corneal precipitates, and it remains to be seen whether fourth-generation fluoroquinolones will have a lower incidence of ocular precipitates.
Ko, Match W L; Dongming Wei; Leung, Christopher K S
Corneal indentation is adapted for the design and development of a characterization method for corneal hysteresis behavior - Corneal Indentation Hysteresis (CIH). Fourteen porcine eyes were tested using the corneal indentation method. The CIH measured in enucleated porcine eyes showed indentation rate and intraocular pressure (IOP) dependences. The CIH increased with indentation rate at lower IOP (<; 25 mmHg) and decreased with indentation rate at higher IOP (> 25 mmHg). The CIH was linear proportional to the IOP within an individual eye. The CIH was positively correlated with the IOP, corneal in-plane tensile stress and corneal tangent modulus (E). A new method based on corneal indentation for the measurement of Corneal Indentation Hysteresis in vivo is developed. To our knowledge, this is the first study to introduce the corneal indentation hysteresis and correlate the corneal indentation hysteresis and corneal tangent modulus.
Theophanous, Christos; Jacobs, Deborah S; Hamrah, Pedram
To illustrate that corneal neuralgia may be the basis for refractory dry eye syndrome after laser-assisted in situ keratomileusis (LASIK). The methodology used is that of a retrospective medical record review of a small case series. Three male patients, aged 30 to 48 years, referred in 2012 for dry eye syndrome refractory to treatment within 1 year of LASIK or LASIK enhancement are reported. Each patient gave history of eye pain, light sensitivity, and difficulty with visual activities beginning within 2 months of LASIK or LASIK enhancement. Best-corrected visual acuity was 20/15 or 20/20 in each of the six eyes. Tear-centered models and metrics did not explain persistent symptoms, which was consistent with inadequate response to standard dry eye treatments used before referral and reported here. In vivo confocal microscopy was abnormal at presentation in each case and was followed over time. Treatments undertaken subsequent to referral included autologous serum tears (three cases), PROSE (Prosthetic Replacement of the Ocular Surface Ecosystem) treatment (two cases), and systemic agents for pain, anxiety, or depression (three cases). By the end of 2013, at a mean of 23 months after LASIK or LASIK enhancement, symptoms improved in all three patients. Patients with persistent dry eye symptoms out of proportion to clinical signs after LASIK have a syndrome that may best be classified as corneal neuralgia. In vivo confocal microscopy can be informative as to the neuropathic basis of this condition. In keeping with current understanding of complex regional pain syndrome, early multimodal treatment directed toward reducing peripheral nociceptive signaling is warranted to avoid subsequent centralization and persistence of pain. Distinguishing this syndrome from typical post-LASIK dry eye remains a challenge.
York, Nicholas J; Tinley, Christopher
Corneal pathology is one of the leading causes of preventable blindness in South Africa (SA). A corneal transplant can restore or significantly improve vision in most cases. However, in SA there is a gross shortage of corneal tissue available to ophthalmologists. Little has been published describing the magnitude of the problem. To describe trends in the number of corneal donors per year in SA, the number of corneal transplants performed each year, the origin of donors, the allocation of corneas to the public or private sector, and the demographics of donors. This was a retrospective review of all corneal donations to SA eye banks over the 15-year period 1 January 2002 - 31 December 2016. There was a progressive year-on-year decline in corneal donors over the study period, from 565 per year in 2002 to 89 in 2016. As a direct result, there has been an 85.5% decrease in the number of corneal transplants performed per year using locally donated corneas, from 1 049 in 2002 to 152 in 2016. Of the donors, 48.8% originated from mortuaries, 39.0% from private hospitals and 12.2% from government hospitals; donors from mortuaries showed the most significant decline over the 15-year period, decreasing by 94.8%. Of donated corneas, 79.3% were allocated to the private sector and 21.7% to the public sector. Males comprised 69.1% of donors, while 77.2% were white, 14.0% coloured, 6.3% black and 2.5% Indian/Asian. Donor age demonstrated a bimodal peak at 25 and 55 years. The number of corneal donations in SA has declined markedly, causing the burden of corneal disease requiring transplantation to rise steadily. Population groups with a low donor rate may have cultural and other objections to corneal donation, which should be a major focus of future research and initiatives aimed at reversing the current trends.
Dong, Nuo; Li, Cheng; Chen, Wen-Sheng; Qin, Wen-Juan; Xue, Yu-Hua; Wu, Hu-Ping
AIM To evaluate the outcomes and safety of lamellar keratoplasty (LK) assisted by fibrin glue in corneal perforations. METHODS Six eyes of 6 patients affected by different corneal pathologies (2 posttraumatic corneal scar and 3 bacterial keratitis) underwent LK procedures by using fibrin glue. The mean corneal perforation diameter was 1.35±0.64mm (range, 0.7-2.5mm), and the greatest diameter of the ulcerative stromal defect was 2.47±0.77mm in average (range, 1.5-3.5mm). The donor corneal lamella diameters were 0.20-mm larger and thicker than the recipient to restore a physiologic corneal thickness and shape: mean donor diameter was 8.34±0.28mm (range, 8.2-8.7mm) and mean thickness was 352±40.27mm (range, 220-400mm). Mean follow-up was 7.33±1.97 months (range, 6-11 months). Postoperatively, the graft status, graft clarity, anterior chamber response, the visual prognosis, intraocular pressures, and postoperative complications were recorded. RESULTS All the corneal perforations were successfully healed after the procedure. The best-corrected visual acuity (BCVA) ranged from 20/1 000 to 20/50 in their initial presentation, and from 20/100 to 20/20 in their last visit, showed increase in all the patients. No major complications such as graft dislocation and graft failure were noted. Neovascularization developed in the superficial stroma of donor graft in 1 case. High intraocular pressure developed on day 2 after surgery, while was remained in normal range after application of anti-glaucomatous eyedrops for 1 week in 1 case. CONCLUSION Fibrin glue-assisted sutureless LK is valuable for maintaining the ocular integrity in the treatment of corneal perforations. PMID:24634865
Raj, K. Mohan; Reddy, P. Arun Subhash; Kumar, Vikram Chella
The corneal arcus consists of cholesterol, phospholipids and triglycerides. As serum triglyceride is one of the accurate of lipid metabolic state, greater importance was given, and it was found to be elevated in 72% of patients and a positive correlation with increasing age. This suggests a strong correlation between impairment of lipid metabolism and incidence of corneal arcus. PMID:26015693
Raj, K Mohan; Reddy, P Arun Subhash; Kumar, Vikram Chella
The corneal arcus consists of cholesterol, phospholipids and triglycerides. As serum triglyceride is one of the accurate of lipid metabolic state, greater importance was given, and it was found to be elevated in 72% of patients and a positive correlation with increasing age. This suggests a strong correlation between impairment of lipid metabolism and incidence of corneal arcus.
Urbanová, Petra; Hejna, Petr; Jurda, Mikoláš
produced high-resolution photorealistic, real sized or easy to calibrate 3D surface models. Both methods equally failed when the scanned body surface was covered with body hair or reflective moist areas. Still, it can be concluded that single camera close range photogrammetry and optical surface scanning using Vectra H1 scanner represent relatively low-cost solutions which were shown to be beneficial for postmortem body documentation in forensic pathology.
Marcon, Alexandre S; Rapuano, Christopher J; Tabas, Janine G
We report a case of a 78-year-old man presenting with 2 discrete areas of sterile corneal melting associated with chronic use of topical ketorolac after uneventful clear corneal phacoemulsification. He was treated successfully with tissue adhesive application. Patients receiving chronic topical ketorolac treatment, especially those with ocular surface abnormalities, can present with severe complications such as corneal melting.
Yokogawa, Hideaki; Sanchez, P James; Mayko, Zachary M; Straiko, Michael D; Terry, Mark A
To calculate the magnitude and angle of the shift in corneal astigmatism associated with Descemet membrane endothelial keratoplasty (DMEK) surgery to determine the feasibility of concurrent astigmatism correction at the time of DMEK triple procedures. Retrospective study. Forty-seven eyes that previously underwent the DMEK procedure for Fuchs endothelial corneal dystrophy and that had more than 1.0 diopter (D) of front corneal astigmatism preoperatively were identified. All DMEK surgeries used a clear corneal temporal incision of 3.2 mm. Surgically induced astigmatism (SIA) was evaluated 6 months postsurgery with vector analysis using Scheimpflug image reading. We did not find a difference between pre- and postoperative magnitude of front astigmatism (P = 0.88; paired t test). The magnitude of the SIA front surface was 0.77 ± 0.63 D (range, 0.10-3.14 D). The centroid vector of the SIA front surface was 0.14 at 89.3°. A hyperopic corneal power shift was noted in both the front surface by 0.26 ± 0.74 D (range, 0.45-3.05 D) (P = 0.018; paired t test) and back surface by 0.56 ± 0.55 D (range, 0.25-2.40 D) (P < 0.01; paired t test). DMEK surgery induces minimal amounts of corneal astigmatism that is a with-the-rule shift associated with a temporal clear corneal incision. The stability of these data from preop to postop supports the plausibility of incorporating astigmatism correction with the cautious use of toric intraocular lenses for patients with Fuchs corneal dystrophy and cataract.
Mo, Juan; Neelam, Sudha; Mellon, Jessamee; Brown, Joseph R.; Niederkorn, Jerry Y.
Purpose Severing corneal nerves during corneal transplantation does not affect first corneal transplants, but abolishes immune privilege of subsequent corneal allografts. This abrogation of immune privilege is attributable to the disabling of T regulatory cells (T regs) induced by corneal transplantation. The goal of this study was to determine if severing corneal nerves induces the development of contrasuppressor (CS) cells, which disable T regs that impair other forms of immune tolerance. Methods Effect of corneal nerve ablation on immune tolerance was assessed in four forms of immune tolerance: anterior chamber–associated immune deviation (ACAID); oral tolerance; corneal transplantation, and intravenously (IV) induced immune tolerance. T regulatory cell activity was assessed by adoptive transfer and by local adoptive transfer (LAT) of suppression assays. Results Corneal nerve ablation prevented ACAID and oral tolerance, but did not affect IV-induced immune tolerance. Contrasuppressor cells blocked the action of T regs that were generated by anterior chamber injection, oral tolerance, or orthotopic corneal transplantation. The neuropeptide substance P (SP) was crucial for contrasuppressor activity as CS cells could not be induced in SP−/− mice and the SP receptor inhibitor, Spantide II, prevented the expression of CS cell activity in vivo. Contrasuppressor cells expressed CD11c surface marker that identifies dendritic cells (DC). Conclusions The loss of immune privilege produced by corneal nerve ablation following corneal transplantation extends beyond the eye and also affects immune tolerance induced through mucosal surfaces and appears to be mediated by a novel cell population of CD11c+ CS cells that disables T regs. PMID:28114571
O'Donnell, Clare; Wolffsohn, James S
To examine the academic literature on the grading of corneal transparency and to assess the potential use of objective image analysis. Reference databases of academic literature were searched and relevant manuscripts reviewed. Annunziato, Efron (Millennium Edition) and Vistakon-Synoptik corneal oedema grading scale images were analysed objectively for relative intensity, edges detected, variation in intensity and maximum intensity. In addition, corneal oedema was induced in one subject using a low oxygen transmissibility (Dk/t) hydrogel contact lens worn for 3h under a light eye patch. Recovery from oedema was monitored over time using ultrasound pachymetry, high and low contrast visual acuity measures, bulbar hyperaemia grading and transparency image analysis of the test and control eyes. Several methods for assessing corneal transparency are described in the academic literature, but none have gained widespread use in clinical practice. The change in objective image analysis with printed scale grade was best described by quadratic parametric or sigmoid 3-parameter functions. 'Pupil image scales' (Annunziato and Vistakon-Synoptik) were best correlated to average intensity; however, the corneal section scale (Efron) was strongly correlated to variations in intensity. As expected, patching an eye wearing a low Dk/t hydrogel contact lens caused a significant (F = 119.2, p < 0.001) 14.3% increase in corneal thickness, which gradually recovered under open eye conditions. Corneal section image analysis was the most affected parameter and intensity variation across the slit width, in isolation, was the strongest correlate, accounting for 85.8% of the variance with time following patching, and 88.7% of the variance with corneal thickness. Corneal oedema is best determined objectively by the intensity variation across the width of a corneal section. This can be easily measured using a slit-lamp camera connected to a computer. Oedema due to soft contact lens wear is not
Abass, Ahmed; Hayes, Sally; White, Nick; Sorensen, Thomas; Meek, Keith M.
It is thought that corneal surface topography may be stabilized by the angular orientation of out-of plane lamellae that insert into the anterior limiting membrane. In this study, micro-focus X-ray scattering data were used to obtain quantitative information about lamellar inclination (with respect to the corneal surface) and the X-ray scatter intensity throughout the depth of the cornea from the centre to the temporal limbus. The average collagen inclination remained predominantly parallel to the tissue surface at all depths. However, in the central cornea, the spread of inclination angles was greatest in the anterior-most stroma (reflecting the increased lamellar interweaving in this region), and decreased with tissue depth; in the peripheral cornea inclination angles showed less variation throughout the tissue thickness. Inclination angles in the deeper stroma were generally higher in the peripheral cornea, suggesting the presence of more interweaving in the posterior stroma away from the central cornea. An increase in collagen X-ray scatter was identified in a region extending from the sclera anteriorly until about 2 mm from the corneal centre. This could arise from the presence of larger diameter fibrils, probably of scleral origin, which are known to exist in this region. Incorporation of this quantitative information into finite-element models will further improve the accuracy with which they can predict the biomechanical response of the cornea to pathology and refractive procedures. PMID:25631562
Abass, Ahmed; Hayes, Sally; White, Nick; Sorensen, Thomas; Meek, Keith M
It is thought that corneal surface topography may be stabilized by the angular orientation of out-of plane lamellae that insert into the anterior limiting membrane. In this study, micro-focus X-ray scattering data were used to obtain quantitative information about lamellar inclination (with respect to the corneal surface) and the X-ray scatter intensity throughout the depth of the cornea from the centre to the temporal limbus. The average collagen inclination remained predominantly parallel to the tissue surface at all depths. However, in the central cornea, the spread of inclination angles was greatest in the anterior-most stroma (reflecting the increased lamellar interweaving in this region), and decreased with tissue depth; in the peripheral cornea inclination angles showed less variation throughout the tissue thickness. Inclination angles in the deeper stroma were generally higher in the peripheral cornea, suggesting the presence of more interweaving in the posterior stroma away from the central cornea. An increase in collagen X-ray scatter was identified in a region extending from the sclera anteriorly until about 2 mm from the corneal centre. This could arise from the presence of larger diameter fibrils, probably of scleral origin, which are known to exist in this region. Incorporation of this quantitative information into finite-element models will further improve the accuracy with which they can predict the biomechanical response of the cornea to pathology and refractive procedures.
Kim, Mee Kum; Hara, Hidetaka
Corneal allo-transplantation is a well-established technique to treat corneal blindness. However, the limited availability of human donors demands the exploration of alternative treatments such as corneal xenotransplantation (e.g., pigs as donors) and bioengineered corneas. Since the first attempt of corneal xenotransplantation using a donor pig cornea in 1844, great advances have been made in the development of genetically-engineered pigs, effective immunosuppressive protocols and the establishment of guidelines for the conduction of clinical trials. We highlight immunological and physio-anatomical barriers of corneal xenotransplantation, recent progress of corneal xenotransplantation in non-human-primates studies, and regulatory guidelines to conduct clinical trials for corneal xenotransplantation.
Rowe, Alexander M.; Yun, Hongmin; Hendricks, Robert L.
Purpose Most of the inflammation in murine herpes simplex virus type 1 (HSV-1)-induced stromal keratitis (HSK) is due to exposure stress resulting from loss of corneal nerves and blink reflex. Corneal grafts often fail when placed on corneal beds with a history of HSK. We asked if corneal exposure contributes to the severe pathology of corneal grafts on HSV-1–infected corneal beds. Methods Herpes simplex virus type 1–infected corneas were tested for blink reflex. Opacity and vascularization were monitored in allogeneic and syngeneic corneal grafts that were transplanted to corneal beds with no blink reflex or to those that retained blink reflex in at least one quadrant following infection. Results Retention of any level of blink reflex significantly reduced inflammation in HSV-1–infected corneas. Corneal allografts placed on HSV-1–infected beds lacking corneal blink reflex developed opacity faster and more frequently than those placed on infected beds that partially or completely retained blink reflex. Corneal grafts placed on infected corneal beds with no blink reflex rapidly became opaque to a level that would be considered rejection. However, protecting these grafts from exposure by tarsorrhaphy prevented or reversed the opacity in both syngeneic and allogenic grafts. Conclusions Exposure due to HSV-1–engendered hypoesthesia causes rapid, severe, persistent, but reversible opacification of both allogeneic and syngeneic corneal grafts. This opacity should not be interpreted as immunologic rejection. Exposure stress may contribute to the high rate of corneal graft pathology in patients with recurrent HSK. PMID:28055100
For almost a century, speech-language pathologists (SLPs) have worked at refining communication disorder phenotypes. Yet a hundred years of mastering the characterization of surface behaviours has provided only limited understanding of the neurobiological underpinnings of communication disorder. Arguably, the most momentous aetiological findings in speech-language pathology have been made relatively recently and by cross-disciplinary colleagues in the fields of molecular genetics and neuroimaging. Such findings include discovery of FOXP2, for example, the first gene found to be associated with a primary speech disorder. New gene-brain-behaviour discoveries in communication disorder are occurring on an almost weekly basis and it is challenging for clinical SLPs to engage with, interpret, and keep abreast of this literature. This paper aims to provide a brief overview of genetic and neuroimaging approaches to the study of communication disorders. Further examples of key findings in these fields are presented, with a discussion of the impacts on core SLP practice. Future research directions for further illuminating gene-brain-behaviour relationships in communication disorder are identified.
Uematsu, Masafumi; Mohamed, Yasser Helmy; Onizuka, Naoko; Ueki, Ryotaro; Inoue, Daisuke; Fujikawa, Azusa; Sasaki, Hitoshi; Kitaoka, Takashi
To evaluate acute corneal permeability changes after instillation of benzalkonium chloride (BAC) using a newly developed in vivo less invasive corneal transepithelial electrical resistance (TER) measurement method in animals and humans. We previously developed an in vivo method for measuring corneal TER using intraocular electrodes in animals. This method can be used to precisely measure the decline of the corneal barrier function after instillation of BAC. To lessen the invasiveness of that procedure, we further refined the method for measuring the corneal TER by developing electrodes that could be placed on the surface of the cornea and in the conjunctival sac instead of inserting them into the anterior chamber. Corneal TER changes before and after exposure to 0.02% BAC were determined in this study using the new device in both rabbits and humans. There was a significant decrease in the corneal TER after exposure of the cornea to 0.02% BAC solution in both rabbits and humans (P<.01). The results of this new less invasive method agreed with those of formerly established anterior chamber methods in rabbit experiments. This new less invasive corneal TER measurement method enables us for the first time to measure TER of the human cornea, allowing safe and reliable investigation of the direct effect of different eye drop treatments on the corneal epithelium. Copyright © 2016 Elsevier Inc. All rights reserved.
Galan, Alessandro; Catania, Anton Giulio; Giudice, Giuseppe Lo
Purpose We describe a case of full-thickness corneal restoration after an acute corneal burn with an acid agent. Methods A 32-year-old male reported painful discomfort, redness, photophobia, and a decrease in visual acuity in the left eye after a unilateral burn with an acid agent. Slit-lamp examination revealed massive corneal melting involving necrotic sequestrum of the entire corneal surface. Surgical approach was carried out in order to preserve residual ocular tissues. Results Extensive corneal–conjunctival layer curettage of the necrotic tissue was performed showing perfectly clear undamaged deep lamellar corneal layers. The patient underwent multilayered amniotic membrane transplantation and total capsular–conjunctival flap in order to preserve ocular tissue from further melting or corneal perforation. A complete and spontaneous “restitutio ad integrum” of the corneal layers was shown during the follow-up. The cornea was perfectly clear with restored normal anatomical architecture. Conclusion In this case, a spontaneous full-thickness corneal tissue restoration occurred after an acute chemical burn. Studies about the mechanisms whereby different cells interact and replicate within the stroma may unveil the biology behind corneal regeneration and transparency. PMID:27194918
Misra, Stuti L; Kersten, Hannah M; Roxburgh, Richard H; Danesh-Meyer, Helen V; McGhee, Charles N J
Ocular surface changes and blink abnormalities are well-established in Parkinson's disease. Blink rate may be influenced by corneal sub-basal nerve density, however, this relationship has not yet been investigated in Parkinson's disease. This case-control study examined the ocular surface in patients with moderately severe Parkinson's disease, including confocal microscopy of the cornea. Fifteen patients with moderately severe Parkinson's disease (modified Hoehn and Yahr grade 3 or 4) and fifteen control participants were recruited. Ophthalmic assessment included slit-lamp examination, blink rate assessment, central corneal aesthesiometry and in vivo corneal confocal microscopy. The effect of disease laterality was also investigated. Of the 15 patients with Parkinson's disease, ten were male and the mean age was 65.5±8.6years. The corneal sub-basal nerve plexus density was markedly reduced in patients with Parkinson's disease (7.56±2.4mm/mm(2)) compared with controls (15.91±2.6mm/mm(2)) (p<0.0001). Corneal sensitivity did not differ significantly between the patients with Parkinson's disease (0.79±1.2mBAR) and the control group (0.26±0.35mBAR), p=0.12. Sub-basal nerve density was not significantly different between the eye ipsilateral to the side of the body with most-severe motor symptoms, and the contralateral eye. There was a significant positive correlation between ACE-R scores and sub-basal corneal nerve density (R(2)=0.66, p=0.02). This is the first study to report a significant reduction in corneal sub-basal nerve density in Parkinson's disease and demonstrate an association with cognitive dysfunction. These results provide further evidence to support the involvement of the peripheral nervous system in Parkinson's disease, previously thought to be a central nervous system disorder.
Lamm, Vladimir; Hara, Hidetaka; Mammen, Alex; Dhaliwal, Deepinder; Cooper, David K C
Approximately 39 million people are blind worldwide, with an estimated 285 million visually impaired. The developing world shoulders 90% of the world's blindness, with 80% of causative diseases being preventable or treatable. Blindness has a major detrimental impact on the patient, community, and healthcare spending. Corneal diseases are significant causes of blindness, affecting at least 4 million people worldwide. The prevalence of corneal disease varies between parts of the world. Trachoma, for instance, is the second leading cause of blindness in Africa, after cataracts, but is rarely found today in developed nations. When preventive strategies have failed, corneal transplantation is the most effective treatment for advanced corneal disease. The major surgical techniques for corneal transplantation include penetrating keratoplasty (PK), anterior lamellar keratoplasty, and endothelial keratoplasty (EK). Indications for corneal transplantation vary between countries, with Fuchs' dystrophy being the leading indication in the USA and keratoconus in Australia. With the exception of the USA, where EK will soon overtake PK as the most common surgical procedure, PK is the overwhelming procedure of choice. Success using corneal grafts in developing nations, such as Nepal, demonstrates the feasibility of corneal transplantation on a global scale. The number of suitable corneas from deceased human donors that becomes available will never be sufficient, and so research into various alternatives, for example stem cells, amniotic membrane transplantation, synthetic and biosynthetic corneas, and xenotransplantation, is progressing. While each of these has potential, we suggest that xenotransplantation holds the greatest potential for a corneal replacement. With the increasing availability of genetically engineered pigs, pig corneas may alleviate the global shortage of corneas in the near future.
Lamm, Vladimir; Hara, Hidetaka; Mammen, Alex; Dhaliwal, Deepinder; Cooper, David K.C.
Approximately 39 million people are blind worldwide, with an estimated 285 million visually impaired. The developing world shoulders 90% of the world’s blindness, with 80% of causative diseases being preventable or treatable. Blindness has a major detrimental impact on the patient, community, and healthcare spending. Corneal diseases are significant causes of blindness, affecting at least 4 million people worldwide. The prevalence of corneal disease varies among parts of the world. Trachoma, for instance, is the second leading cause of blindness in Africa, after cataracts, but is rarely found today in developed nations. When preventive strategies have failed, corneal transplantation is the most effective treatment for advanced corneal disease. The major surgical techniques for corneal transplantation include penetrating keratoplasty (PK), anterior lamellar keratoplasty (ALK), and endothelial keratoplasty (EK). Indications for corneal transplantation vary among countries, with Fuchs’ dystrophy being the leading indication in the U.S. and keratoconus in Australia. With the exception of the US, where EK will soon overtake PK as the most common surgical procedure, PK is the overwhelming procedure of choice. Success using corneal grafts in developing nations, such as Nepal, demonstrates the feasibility of corneal transplantation on a global scale. The number of suitable corneas from deceased human donors that becomes available will never be sufficient, and so research into various alternatives, e.g., stem cells, amniotic membrane transplantation, synthetic and biosynthetic corneas, and xenotransplantation, is progressing. While each of these has potential, we suggest that xenotransplantation holds the greatest potential for a corneal replacement. With the increasing availability of genetically-engineered pigs, pig corneas may alleviate the global shortage of corneas in the near future. PMID:25268248
Klijn, Stijn; Reus, Nicolaas J; van der Sommen, Charlotte M; Sicam, Victor Arni D P
To determine the accuracy of total corneal astigmatism measurements with a Scheimpflug imager and a color light-emitting diode corneal topographer, and to compare the accuracy of total corneal astigmatism measurements with the accuracy of measurements that are based only on the anterior corneal surface. Prospective validity assessment. This study was conducted at the Rotterdam Ophthalmic Institute, Rotterdam, Netherlands. The study population consisted of 91 eyes of 91 patients with monofocal, non-toric intraocular lenses (IOLs). Refractive astigmatism was measured with the ARK-530A autorefractor (Nidek, Gamagori, Japan). Anterior and total corneal astigmatism were measured with the Pentacam HR (Oculus, Wetzlar, Germany) and the Cassini (i-Optics, The Hague, Netherlands). Under the assumption that refractive astigmatism must equal total corneal astigmatism in these patients, accuracy of the corneal astigmatism measurements was defined as the vectorial difference with the refractive astigmatism, with lower vector differences denoting higher accuracy. The median refractive astigmatic magnitude was 0.84 diopter (D). The mean difference vector lengths were 0.61 D, 0.58 D, 0.49 D, and 0.45 D for Pentacam anterior, Cassini anterior, Pentacam total, and Cassini total corneal astigmatism, respectively. The mean difference vector length decreased by 0.12 and 0.13 D for Pentacam and Cassini, respectively, if the total instead of anterior corneal astigmatism was measured. These decreases were statistically significant (P < .001). With Pentacam as well as with Cassini, the accuracy of total corneal astigmatism measurements was higher than that of anterior corneal astigmatism measurements. Measuring total instead of anterior corneal astigmatism may therefore decrease the residual astigmatism in toric IOL implantation. Copyright © 2016 Elsevier Inc. All rights reserved.
Koizumi, Noriko; Okumura, Naoki; Kinoshita, Shigeru
This review describes our recent attempts to develop new therapeutic modalities for corneal endothelial disease using animal models including non-human primate model in which the proliferative ability of corneal endothelial cells is severely limited, as is the case in humans. First, we describe our attempt to develop new surgical treatments using cultivated corneal endothelial cells for advanced corneal endothelial dysfunction. It includes two different approaches; a "corneal endothelial cell sheet transplantation" with cells grown on a type-I collagen carrier, and a "cell-injection therapy" combined with the application of Rho-kinase (ROCK) inhibitor. Recently, it was reported that the selective ROCK inhibitor, Y-27632, promotes cell adhesion and proliferation and inhibits the apoptosis of primate corneal endothelial cells in culture. When cultivated corneal endothelial cells were injected into the anterior chamber of animal eyes in the presence of ROCK inhibitor, endothelial cell adhesion was promoted and the cells achieved a high cell density and a morphology similar to corneal endothelial cells in vivo. We are also trying to develop a novel medical treatment for the early phase of corneal endothelial disease by the use of ROCK inhibitor eye drops. In rabbit and monkey experiments using partial endothelial dysfunction models, corneal endothelial wound healing was accelerated by the topical application of ROCK inhibitor to the ocular surface, and resulted in the regeneration of a corneal endothelial monolayer with a high endothelial cell density. We are now trying to advance the clinical application of these new therapies for patients with corneal endothelial dysfunction. Copyright © 2011 Elsevier Ltd. All rights reserved.
Krachmer, J H
Pellucid marginal degeneration of the cornea is a bilateral, clear, inferior, peripheral corneal-thinning disorder. Protrusion of the cornea occurs above a band of thinning, which is located 1 to 2 mm from the limbus and measures 1 to 2 mm in width. American ophthalmologists are generally not familiar with the condition because most of the literature concerning pellucid degeneration is European. Four cases are described. This condition is differentiated from other noninflammatory cornel-thinning disorders such as keratoconus, keratoglobus, keratotorus, and posterior keratoconus. It is also differentiated from peripheral corneal disorders associated with inflammation such as Terrien's peripheral corneal degeneration, Mooren's ulcers, and ulcers from connective tissue disease.
Mahelkova, Gabriela; Jirsova, Katerina; Seidler Stangova, Petra; Palos, Michalis; Vesela, Viera; Fales, Ivan; Jiraskova, Nada; Dotrelova, Dagmar
In vivo corneal confocal microscopy allows the examination of each layer of the cornea in detail and the identification of pathological changes at the cellular level. The purpose of this study was to identify the possible effects of a three-month treatment with autologous serum eye-drops in different corneal layers of patients with severe dry eye disease using corneal confocal microscopy. Twenty-six patients with dry eye disease were included in the study. Corneal fluorescein staining was performed. The corneas of the right eyes were examined using in vivo corneal confocal microscopy before and after a three-month treatment with autologous serum drops. The densities of superficial and basal epithelial cells, Langerhans cells, the keratocytes and activated keratocytes, the density of endothelial cells and the status of the sub-basal nerve plexus fibres were evaluated. A significant decrease in corneal fluorescein staining was found after the three-month autologous serum treatment (p = 0.0006). The basal epithelial cell density decreased significantly (p = 0.001), while the density of superficial epithelial cells did not change significantly (p = 0.473) nor did the number of Langerhans cells or activated keratocytes (p = 0.223; p = 0.307, respectively). There were no differences in the other corneal cell layers or in the status of the nerve fibres. The results demonstrate the ability of corneal confocal microscopy to evaluate an improvement in the basal epithelial cell layer of the cornea after autologous serum treatment in patients with dry eye disease. More studies with longer follow-up periods are needed to elucidate the suitability of corneal confocal microscopy to follow the effect of autologous serum treatment on nerve fibres or other corneal layers in dry eye disease patients. © 2016 Optometry Australia.
Wilhelmus, Kirk R; Abshire, Robert L
To examine how age affects the risk of developing a white corneal precipitate during ciprofloxacin therapy for bacterial keratitis and to explore the effect of a white precipitate on rates of clinical improvement and cure. Prospective, multicenter, observational cohort study. Occurrence of a white precipitate of the corneal surface was recorded among 624 patients with presumed bacterial keratitis who were treated with topical ciprofloxacin 0.3% solution or ointment. Relative risks of corneal precipitation were estimated from logistic regression for age categories and other clinical characteristics. The time-dependent effects of precipitate on rates of infection resolution and corneal reepithelialization were estimated by proportional hazards regression. Ninety-five (15.2%) patients developed a white corneal precipitate during ciprofloxacin therapy; 72 (75.8%) began within the first 3 days of treatment. Compared with those younger than 40 years old, patients aged 60 to 69 years had 2.8 (95% confidence limits [CL], 1.9, 3.9) times the risk of ciprofloxacin precipitation; patients 70 years and older had 3.7 (95% CL, 2.6, 5.0) times the risk. Median duration of the visible corneal precipitate was 8.5 days (90% decile, 32 days). Presence of ciprofloxacin precipitation did not significantly affect the time until therapeutic improvement (P =.09) but slowed the time until reepithelialization by 55% (95% CL 32%, 70%). Older patients treated with topical ciprofloxacin for bacterial keratitis have a higher risk of corneal deposition. A white precipitate apparently does not interfere with antibacterial therapeutic response but may delay epithelial healing of ulcerative keratitis.
Zakaria, Nadia; Van Grasdorff, Sigi; Wouters, Kristien; Rozema, Jos; Koppen, Carina; Lion, Eva; Cools, Nathalie; Berneman, Zwi; Tassignon, Marie-José
Corneal neovascularization results from the encroachment of blood vessels from the surrounding conjunctiva onto the normally avascular cornea. The aim of this study is to identify factors in human tears that are involved in development and/or maintenance of corneal neovascularization in humans. This could allow development of diagnostic tools for monitoring corneal neovascularization and combination monoclonal antibody therapies for its treatment. In an observational case-control study we enrolled a total of 12 patients with corneal neovascularization and 10 healthy volunteers. Basal tears along with reflex tears from the inferior fornix, superior fornix and using a corneal bath were collected along with blood serum samples. From all patients, ocular surface photographs were taken. Concentrations of the pro-angiogenic cytokines interleukin (IL)-6, IL-8, Vascular Endothelial Growth Factor (VEGF), Monocyte Chemoattractant Protein 1 (MCP-1) and Fas Ligand (FasL) were determined in blood and tear samples using a flow cytometric multiplex assay. Our results show that the concentration of pro-angiogenic cytokines in human tears are significantly higher compared to their concentrations in serum, with highest levels found in basal tears. Interestingly, we could detect a significantly higher concentration of IL- 6, IL-8 and VEGF in localized corneal tears of patients with neovascularized corneas when compared to the control group. This is the first study of its kind demonstrating a significant difference of defined factors in tears from patients with neovascularized corneas as compared to healthy controls. These results provide the basis for future research using animal models to further substantiate the role of these cytokines in the establishment and maintenance of corneal neovascularization.
Wouters, Kristien; Rozema, Jos; Koppen, Carina; Lion, Eva; Cools, Nathalie; Berneman, Zwi; Tassignon, Marie-José
Corneal neovascularization results from the encroachment of blood vessels from the surrounding conjunctiva onto the normally avascular cornea. The aim of this study is to identify factors in human tears that are involved in development and/or maintenance of corneal neovascularization in humans. This could allow development of diagnostic tools for monitoring corneal neovascularization and combination monoclonal antibody therapies for its treatment. In an observational case-control study we enrolled a total of 12 patients with corneal neovascularization and 10 healthy volunteers. Basal tears along with reflex tears from the inferior fornix, superior fornix and using a corneal bath were collected along with blood serum samples. From all patients, ocular surface photographs were taken. Concentrations of the pro-angiogenic cytokines interleukin (IL)-6, IL-8, Vascular Endothelial Growth Factor (VEGF), Monocyte Chemoattractant Protein 1 (MCP-1) and Fas Ligand (FasL) were determined in blood and tear samples using a flow cytometric multiplex assay. Our results show that the concentration of pro-angiogenic cytokines in human tears are significantly higher compared to their concentrations in serum, with highest levels found in basal tears. Interestingly, we could detect a significantly higher concentration of IL- 6, IL-8 and VEGF in localized corneal tears of patients with neovascularized corneas when compared to the control group. This is the first study of its kind demonstrating a significant difference of defined factors in tears from patients with neovascularized corneas as compared to healthy controls. These results provide the basis for future research using animal models to further substantiate the role of these cytokines in the establishment and maintenance of corneal neovascularization. PMID:22590547
Nearsightedness surgery - discharge; Refractive surgery - discharge; LASIK - discharge; PRK - discharge ... You had refractive corneal surgery to help improve your vision. This surgery uses a laser to reshape your cornea. It corrects mild-to-moderate nearsightedness, ...
Elhalis, Hussain; Azizi, Behrooz; Jurkunas, Ula V.
Fuchs endothelial corneal dystrophy (FECD) is characterized by progressive loss of corneal endothelial cells, thickening of Descement’s membrane and deposition of extracellular matrix in the form of guttae. When the number of endothelial cells becomes critically low, the cornea swells and causes loss of vision. The clinical course of FECD usually spans 10–20 years. Corneal transplantation is currently the only modality used to restore vision. Over the last several decades genetic studies have detected several genes, as well as areas of chromosomal loci associated with the disease. Proteomic studies have given rise to several hypotheses regarding the pathogenesis of FECD. This review expands upon the recent findings from proteomic and genetic studies and builds upon recent advances in understanding the causes of this common corneal disorder. PMID:20964980
... ency/presentations/100082.htm Corneal transplant - series—Normal anatomy To use the sharing features on this page, ... Bethesda, MD 20894 U.S. Department of Health and Human Services National Institutes of Health Page last updated: ...
Denis, Heidi M
Corneal disease is common in equine ophthalmology and requires vigilant monitoring and appropriate therapy to optimize the outcome. Many equine corneal diseases, particularly those that progress rapidly, may benefit from surgical intervention. These include descemetoceles, deep corneal lacerations and ulcers, corneal perforation/iris prolapse, ulcerative keratitis, corneal stromal abscesses, and corneoscleral neoplasia. Indications for corneal transplantation include optical, tectonic, therapeutic, and cosmetic purposes. Corneal transplantation is most often implemented in equine patients for tectonic and therapeutic reasons when a cornea is compromised by corneal stromal abscess, iris prolapse, or neoplasia. This article provides an outline of when to consider surgical intervention for corneal disease, the procedures available and expected outcomes, and how appropriate early surgical intervention can dramatically improve the end result.
van Bijsterveld, O P
Central corneal abscess developed in the experimental animal after inoculation of biologically active staphylococcal strains in a paracentral epithelial lesion of the cornea. These abscesses did not ulcerate, developed only with high inocula, occurred more frequently in immunized rabbits. A serpiginous type of ulceration did not develop at the site of the initial epithelial lesion nor at any other place in the cornea. Histologically, the lesions consisted of densely packed polymorphonuclear leukocytes between the corneal lamellae.
Fielder, A R; Winder, A F; Sheraidah, G A; Cooke, E D
Corneal arcus presents many puzzling features. The correlation between its incidence and serum lipid levels is poor and, using immunoelectrophoresis, we have only been able to identify low-density lipoprotein inconsistently in corneae containing this deposition. Infrared thermography has shown us that arcus commences in the warmest regions of the cornea. We have considered the possible relevance of our biochemical and thermographic findings to other problems with corneal arcus such as its irreversibility, anatomical distribution, and clear zone.
Gao, Feng; Lin, Tao; Pan, Yingzhe
Diabetic keratopathy is an ocular complication that occurs with diabetes. In the present study, the effect of diabetic keratopathy on corneal optical density, central corneal thickness, and corneal endothelial cell count was investigated. One hundred and eighty diabetic patients (360 eyes) were enrolled in the study during the period from March, 2012 to March, 2013. The patients were divided into three age groups: <5, 5-10 and >10 years, with 60 patients per group (120 eyes). During the same period, 60 healthy cases (120 eyes) were selected and labeled as the normal control group. The Pentacam was used to measure the corneal optical density, and central corneal thickness. Specular microscopy was used to examine the corneal endothelial cell density. The coefficient of partial correlation was used to control age and correlate the analysis between the corneal optical density, corneal endothelial cell density, and central corneal thickness. The stage of the disease, the medial and intimal corneal optical density and central corneal thickness was analyzed in the diabetes group. The corneal optical density in the diabetes group increased compared with that of the normal control group. The medial and intimal corneal optical density and central corneal thickness were positively correlated with the course of the disease. However, the corneal endothelial cell density was not associated with the course of diabetes. There was a positive association between the medial and intimal corneal optical density and central corneal thickness of the diabetic patients. In conclusion, the results of the present study show that medial and intimal corneal optical density and central corneal thickness were sensitive indicators for early diabetic keratopathy.
Gao, Feng; Lin, Tao; Pan, Yingzhe
Diabetic keratopathy is an ocular complication that occurs with diabetes. In the present study, the effect of diabetic keratopathy on corneal optical density, central corneal thickness, and corneal endothelial cell count was investigated. One hundred and eighty diabetic patients (360 eyes) were enrolled in the study during the period from March, 2012 to March, 2013. The patients were divided into three age groups: <5, 5–10 and >10 years, with 60 patients per group (120 eyes). During the same period, 60 healthy cases (120 eyes) were selected and labeled as the normal control group. The Pentacam was used to measure the corneal optical density, and central corneal thickness. Specular microscopy was used to examine the corneal endothelial cell density. The coefficient of partial correlation was used to control age and correlate the analysis between the corneal optical density, corneal endothelial cell density, and central corneal thickness. The stage of the disease, the medial and intimal corneal optical density and central corneal thickness was analyzed in the diabetes group. The corneal optical density in the diabetes group increased compared with that of the normal control group. The medial and intimal corneal optical density and central corneal thickness were positively correlated with the course of the disease. However, the corneal endothelial cell density was not associated with the course of diabetes. There was a positive association between the medial and intimal corneal optical density and central corneal thickness of the diabetic patients. In conclusion, the results of the present study show that medial and intimal corneal optical density and central corneal thickness were sensitive indicators for early diabetic keratopathy. PMID:27588090
Teoh, Stephen C B; Lee, Jong-Jian; Fam, Han-Bor
We report the complications and management of a retained bee sting injury to the cornea. The case highlights the acute and chronic management of an uncommon injury and its pathogenesis. A 67-year-old man was attacked by a swarm of bees and was referred for severe chemosis on the right eye. A retained corneal bee stinger (ovipositor) was seen but removal was only partially successful. He subsequently developed a large corneal epithelial defect, anterior uveitis, intractable glaucoma, traumatic cataract, toxic optic neuropathy, and corneal scarring. We reviewed the literature on corneal bee sting injuries and their complications. Inflammation was controlled with topical steroids and the patient underwent a combined phacoemulsification and trabeculectomy with mitomycin-C for uncontrolled glaucoma. However, optic neuropathy did not resolve. Corneal bee sting injuries are uncommon but can result in severe sight-threatening complications such as toxic optic neuropathy. Early recognition of the possible complications and appropriate treatment may help to prevent permanent loss of vision. Removal of a retained corneal bee stinger remains controversial.
Savini, Giacomo; Calossi, Antonio; Camellin, Massimo; Carones, Francesco; Fantozzi, Marco; Hoffer, Kenneth J
To evaluate whether the refractive changes induced by excimer laser surgery can be accurately measured by corneal ray tracing performed by a combined rotating Scheimpflug camera-Placido-disk corneal topographer (Sirius). Private practices. Evaluation of diagnostic test. This multicenter retrospective study comprised patients who had myopic or hyperopic excimer laser refractive surgery. Preoperatively and postoperatively, 2 corneal power measurements--simulated keratometry (K) and mean pupil power--were obtained. The mean pupil power was the corneal power calculated over the entrance pupil by ray tracing through the anterior and posterior corneal surfaces using Snell's law. Agreement between the refractive and corneal power change was analyzed according to Bland and Altman. Regression analysis and Bland-Altman plots were used to evaluate agreement between measurements. The study evaluated 72 eyes (54 patients). The difference between the postoperative and preoperative simulated K values underestimated the refractive change after myopic correction and overestimated it after hyperopic correction. Agreement between simulated K changes and refractive changes was poor, especially for higher amounts of correction. A proportional bias was detected (r = -0.77; P<.0001), and the 95% limits of agreement (LoA) were -0.15 -0.14 × ±0.62 diopters (D). The difference between the postoperative and preoperative mean pupil power showed an excellent correlation with the refractive change (r(2) = 0.98). The mean pupil power did not overestimate or underestimate the refractive change. The 95% LoA ranged between -0.97 D and +0.56 D. Corneal ray tracing accurately measured corneal power changes after excimer laser refractive surgery. Dr. Calossi is consultant to Costruzione Strumenti Oftalmici. Dr. Carones is consultant to Wavelight Laser Technologie AG. No other author has a financial or proprietary interest in any material or method mentioned. Copyright © 2014 ASCRS and ESCRS
Swinger, C A; Kornmehl, E W; York, S; Forman, J S
A corneal mold is described that provides an MK corneal button of normal thickness and curvature from an edematous, post-mortem button. The uniform, processed tissue can then be used for experimental refractive surgery.
Arvola, Riku P J; Robciuc, Alexandra; Holopainen, Juha M
Treating corneal neurotrophic ulcers is challenging. Topical application of matrix regeneration therapy (RGTA), which is a dextran derivative polymer and heparan sulfate analog, is a promising regenerative therapy and an alternative or additional therapeutic regimen when corneal healing is compromised. The aim of this study was to evaluate the efficacy of RGTA (Cacicol) in the treatment of 6 patients with severe neurotrophic ulcers. We present an uncontrolled prospective case series of 6 patients (6 eyes) with severe corneal neurotrophic ulcers. Patients were treated with topical RGTA at a dose of 1 drop every second day. The main outcome measure was complete corneal epithelialization. We measured corneal thickness by anterior segment swept-source optical coherence tomography. Two patients (33%) showed complete corneal healing, one at 6 weeks and the other at 10 weeks. Treatment was considered failure in 4 patients (67%), and 1 patient had corneal perforation. None of the patients showed improvement in best-corrected visual acuity. There were no RGTA-related local or systemic side effects. Based on previous studies, RGTA seems to be a promising therapeutic agent for controlling ocular surface inflammation and promoting corneal healing. In this study, the efficacy of RGTA did not match the encouraging results from previous reports.
Resch, Miklós D.; Marsovszky, László; Németh, János; Bocskai, Márta; Kovács, László
Purpose. Investigation of dry eye and corneal Langerhans cells (LCs) in systemic lupus erythematosus (SLE). Methods. Prospective consecutive case series of 27 SLE patients and 27 control subjects. Dry eye was evaluated by lid-parallel conjunctival folds (LIPCOF), Schirmer test, tear break-up time (TBUT), and ocular surface disease index (OSDI) questionnaire. In vivo investigation of corneal LCs density and morphology (LCM) was performed with confocal corneal microscopy (Heidelberg Retina Tomograph with Rostock Cornea Module). Results. Tear production and stability were pathological in SLE subjects compared to control (Schirmer: 8.45 ± 9.82 mm/5 min versus 11.67 ± 3.21 mm/5 min; TBUT: 6.86 ± 3.53 s versus 11.09 ± 3.37 s). OSDI was significantly greater in SLE patients (25.95 ± 17.92) than in controls (11.06 ± 7.18). Central LC density was greater in SLE patients (43.08 ± 48.67 cell/mm2) than in controls (20.57 ± 21.04 cell/mm2). There was no difference in the peripheral LC density (124.78 ± 165.39 versus 78.00 ± 39.51 cell/mm2). LCM was higher in SLE patients in the centre (1.43 ± 0.79) and in the periphery (2.89 ± 0.42) compared to controls (centre: 1.00 ± 0.69, periphery: 2.35 ± 0.54). Conclusions. Significant changes in dry eye parameters and marked increase of central LCs could be demonstrated in SLE patients. SLE alters not only the LC density but also the morphology, modifies corneal homeostasis, and might contribute to the development of dry eye. PMID:25893112
Resch, Miklós D; Marsovszky, László; Németh, János; Bocskai, Márta; Kovács, László; Balog, Attila
Purpose. Investigation of dry eye and corneal Langerhans cells (LCs) in systemic lupus erythematosus (SLE). Methods. Prospective consecutive case series of 27 SLE patients and 27 control subjects. Dry eye was evaluated by lid-parallel conjunctival folds (LIPCOF), Schirmer test, tear break-up time (TBUT), and ocular surface disease index (OSDI) questionnaire. In vivo investigation of corneal LCs density and morphology (LCM) was performed with confocal corneal microscopy (Heidelberg Retina Tomograph with Rostock Cornea Module). Results. Tear production and stability were pathological in SLE subjects compared to control (Schirmer: 8.45 ± 9.82 mm/5 min versus 11.67 ± 3.21 mm/5 min; TBUT: 6.86 ± 3.53 s versus 11.09 ± 3.37 s). OSDI was significantly greater in SLE patients (25.95 ± 17.92) than in controls (11.06 ± 7.18). Central LC density was greater in SLE patients (43.08 ± 48.67 cell/mm(2)) than in controls (20.57 ± 21.04 cell/mm(2)). There was no difference in the peripheral LC density (124.78 ± 165.39 versus 78.00 ± 39.51 cell/mm(2)). LCM was higher in SLE patients in the centre (1.43 ± 0.79) and in the periphery (2.89 ± 0.42) compared to controls (centre: 1.00 ± 0.69, periphery: 2.35 ± 0.54). Conclusions. Significant changes in dry eye parameters and marked increase of central LCs could be demonstrated in SLE patients. SLE alters not only the LC density but also the morphology, modifies corneal homeostasis, and might contribute to the development of dry eye.
Micali, Jason Daniel
The cornea is the anterior most surface of the eye and plays a critical role in vision. A thin fluid layer, the tear film, coats the outer surface of the cornea and serves to protect, nourish, and lubricate the cornea. At the same time, the tear film is responsible for creating a smooth continuous surface where the majority of refraction takes place in the eye. A significant component of vision quality is determined by the shape of the cornea and stability of the tear film. It is desirable to possess an instrument that can measure the corneal shape and tear film surface with the same accuracy and resolution that is currently performed on common optical elements. A dual interferometer system for measuring the dynamic corneal topography is designed, built, and verified. The completed system is validated by testing on human subjects. The system consists of two co-aligned polarization splitting Twyman-Green interferometers designed to measure phase instantaneously. The primary interferometer measures the surface of the tear film while the secondary interferometer simultaneously tracks the absolute position of the cornea. Eye motion, ocular variation, and a dynamic tear film surface will result in a non-null configuration of the surface with respect to the interferometer system. A non-null test results in significant interferometer induced errors that add to the measured phase. New algorithms are developed to recover the absolute surface topography of the tear film and corneal surface from the simultaneous interferometer measurements. The results are high-resolution and high-accuracy surface topography measurements of the in vivo cornea that are captured at standard camera frame rates. This dissertation will cover the development and construction of an interferometer system for measuring the dynamic corneal topography of the human eye. The discussion starts with the completion of an interferometer for measuring the tear film. The tear film interferometer is part of an
Strong, Travis D; Tangeman, Sarah; Ben-Shlomo, Gil; Haynes, Joseph; Allbaugh, Rachel A
To present the clinicopathologic features of a Domestic Short-haired cat with spontaneous, intermediate-grade corneal fibrosarcoma, possibly secondary to chronic corneal irritation associated with a corneal sequestrum. A 12-year-old, spayed female Domestic Short-haired cat was evaluated for a slowly growing, pink, exophytic mass affecting the left cornea. The cat had presented 6 years previously for bilateral brown corneal sequestra, as well as 3 years previously for a small pale growth on the left cornea hypothesized to be an epithelial inclusion cyst and a corneal ulcer affecting the right eye. Incisional biopsy of the corneal mass indicated intermediate-grade corneal fibrosarcoma within the corneal stroma. Owing to the potential for malignant behavior, the left globe was enucleated. Routine systemic staging was performed prior to surgery with no evidence of metastasis. Definitive diagnosis of corneal fibrosarcoma was made through histopathologic examination of the incisional biopsy. There was an elevated mitotic index, indicating an intermediate-grade phenotype. Histopathology of the enucleated globe substantiated the initial findings, and complete tumor resection was confirmed. Subjacent to the corneal fibrosarcoma, there was a region of necrotic tissue suggestive of a corneal sequestrum. Six months after diagnosis and enucleation, the patient remained healthy with no signs of local spread or distant metastasis. To the authors' knowledge, this is the first documented case of a corneal fibrosarcoma in a cat. © 2016 American College of Veterinary Ophthalmologists.
Ventura, Liliane; Chiaradia, Caio; Faria de Sousa, Sidney J.
A very common disease in agricultural countries is the corneal ulcer. Particularly in the public hospitals, several patients come every week presenting this kind of pathology. One of the most important features to diagnose the regression of the disease is the determination of the vanishing of the affected area. An automatic system (optical system and software), attached to a Slit Lamp, has been developed to determine automatically the area of the ulcer and to follow up its regression. The clinical procedure to isolate the ulcer is still done, but the measuring time is fast enough to not cause discomfort to the patient as the traditional evaluation does. The system has been used in the last 6 months in a hospital that has about 80 patients per week presenting corneal ulcer. The patients follow up (which is an indispensable criteria for the cure of the disease) has been improved by the system and has guaranteed the treatment success.
Purpose. To compare the change of anterior corneal higher-order aberrations (HOAs) after laser in situ keratomileusis (LASIK), wavefront-guided LASIK with iris registration (WF-LASIK), femtosecond laser-assisted laser in situ keratomileusis (FS-LASIK), and small incision lenticule extraction (SMILE). Methods. In a prospective study, 82 eyes underwent LASIK, 119 eyes underwent WF-LASIK, 88 eyes underwent FS-LASIK, and 170 eyes underwent SMILE surgery. HOAs were measured with Pentacam device preoperatively and 6 months after surgery. The aberrations were described as Zernike polynomials, and analysis focused on total HOAs, spherical aberration (SA), horizontal coma, and vertical coma over 6 mm diameter central corneal zone. Results. Six months postoperatively, all procedures result in increase of anterior corneal total HOAs and SA. There were no significant differences in the induced HOAs between LASIK and FS-LASIK, while SMILE induced fewer total HOAs and SA compared with LASIK and FS-LASIK. Similarly, WF-LASIK also induced less total HOAs than LASIK and FS-LASIK, but only fewer SA than FS-LASIK (P < 0.05). No significant difference could be detected in the induced total HOAs and SA between SMILE and WF-LASIK, whereas SMILE induced more horizontal coma and vertical coma compared with WF-LASIK (P < 0.05). Conclusion. FS-LASIK and LASIK induced comparable anterior corneal HOAs. Compared to LASIK and FS-LASIK, both SMILE and WF-LASIK showed advantages in inducing less total HOAs. In addition, SMILE also possesses better ability to reduce the induction of SA in comparison with LASIK and FS-LASIK. However, SMILE induced more horizontal coma and vertical coma compared with WF-LASIK, indicating that the centration of SMILE procedure is probably less precise than WF-LASIK. PMID:27818792
Pitz, S; Jahn, R; Frisch, L; Duis, A; Pfeiffer, N
Background: The performance and results of corneal tattooing are described in a case series of 11 patients suffering from a disfiguring corneal scar using a technique similar to conventional dermatography. Methods: Drawing ink in different shades was applied into the anterior corneal stroma by punctures performed with a conventional spatula needle. Results: Up to 4 years after surgery all patients still had satisfactory staining of the formerly cosmetically disfiguring corneal scar. Conclusion: Tattooing of unsightly corneal scars proved to be an efficient and easy to perform technique, yielding acceptable results during follow up. PMID:11914207
Zhao, Ran; Di, La-na; Zhao, Xiao-zhuo; Wang, Cheng; Zhang, Guo-an
Airway tissue shows unexpected invulnerability to heated air. The mechanisms of this phenomenon are open to debate. This study was designed to measure the surface temperatures at different locations of the airway, and to explore the relationship between the tissue's surface temperature and injury severity. Twenty dogs were randomly divided into four groups, including three experimental groups (six dogs in each) to inhale heated air at 70-80 °C (group I), 150-160 °C (group II) and 310-320 °C (group III) and a control group (two dogs, only for histological observation). Injury time was 20 min. Mucosal surface temperatures of the epiglottis (point A), cricoid cartilage (point B) and lower trachea (point C) were measured. Dogs in group I-III were divided into three subgroups (two in each), to be assayed at 12, 24 and 36 h after injury, respectively. For each dog, four tissue parts (epiglottis, larynx, lower trachea and terminal bronchiole) were microscopically observed and graded according to an original pathological scoring system (score range: 0-27). Surface temperatures of the airway mucosa increased slowly to 40.60±3.29 °C, and the highest peak temperature was 48.3 °C (group III, point A). The pathological score of burned tissues was 4.12±4.94 (0.0-18.0), suggesting slight to moderate injuries. Air temperature and airway location both influenced mucosal temperature and pathological scores very significantly, and there was a very significant positive correlation between tissue temperature and injury severity. Compared to the inhalational air hyperthermia, airway surface temperature was much lower, but was still positively correlated with thermal injury severity. Copyright © 2012 Elsevier Ltd and ISBI. All rights reserved.
Sayegh, Samir I.
Refractive surgeons and cataract surgeons need accurate measurements of corneal curvature/power. Increased expectations of patients, the increasing number of patients having undergone prior surgeries and patients with corneal pathologies dictate the need for reliable curvature measurements to enhance the predictability and the quality of surgical outcomes. Eye movements can negatively influence these measurements. We present a model of eye movements based on peak saccade velocities and formulate criteria for obtaining OCT topography within ¼ of a diopter. Using these criteria we illustrate how next generation MHz systems will allow full corneal OCT topography in both healthy and pathological corneas
Ehlers, Niels; Hjortdal, Jesper; Nielsen, Kim
Corneal transplantation was conceptualized at the end of the 18th century, but it took more than 100 years before human corneal grafting was introduced. The greatest step forward was the demonstration by Filatov that corneal tissue can be collected and used post mortem. The history of eye banking includes the development of preservation techniques. Storage in cold to minimize microbial growth and tissue disintegration was first choice but during the last 30 years this has been taken over by warm storage (organ culture) where the donor cornea proves its sterility and vitality before being transferred to the recipient. The long-term organ culture storage makes exchange between centres possible and allows for histocompatibility matching. The internationalization led to the establishing of the European Eye Bank Association but also to an increasing number of governmental regulations. Developments in years to come may lead to control of graft biomechanics and optics. This technical development tends to favour a centralization.
Compañ, Vicente; Aguilella-Arzo, Marcel; Edrington, Timothy B; Weissman, Barry A
The main goal of this current work is to use an updated calculation paradigm, and updated boundary conditions, to provide theoretical guidelines to assist the clinician whose goal is to improve his or her scleral gas permeable (GP) contact lens wearing patients' anterior corneal oxygen supply. Our model uses a variable value of corneal oxygen consumption developed through Monod equations that disallows negative oxygen tensions within the stroma to predict oxygen tension at the anterior corneal surface of scleral GP contact lens wearing eyes, and to describe oxygen tension and flux profiles, for various boundary conditions, through the lens, tears, and cornea. We use several updated tissue and boundary parameters in our model. Tear exchange with GP scleral lenses is considered nonexistent in this model. The majority of current scleral GP contact lenses should produce some levels of corneal hypoxia under open eye conditions. Only lenses producing the thinnest of tear vaults should result in anterior corneal surface oxygen tensions greater than a presumed critical oxygen tension of 100 mmHg. We also find that corneal oxygen tension and flux are each more sensitive to modification in tear vault than to changes in lens oxygen permeability, within the ranges of current clinical manipulation. Our study suggests that clinicians would be prudent to prescribe scleral GP lenses manufactured from higher oxygen permeability materials and especially to fit without excessive corneal clearance.
Kaufmann, C; Bochmann, F; Baenninger, P; Thiel, M A
Combined excimer laser correction and corneal cross-linking is a promising concept in treating keratoconus patients. Central corneal regularization represents advanced topography-guided custom ablation for ectatic corneas, aiming at correcting irregular astigmatism and at increasing the optical regularity of the corneal surface. In a prospective single centre study, 10 keratoconus patients underwent combined treatment with corneal cross-linking and central corneal regularization by an iRES-Laser. Uncorrected visual acuity at 1 and 3 months postoperatively represented the primary endpoint. Mean preoperative uncorrected decimal visual acuity was 0.15 (± 0.28 standard deviation). Mean postoperative visual acuity was 0.28 (± 0.47) at one month and 0.24 (± 0.25) at three months, respectively. Combined corneal cross-linking and central corneal regularization treatment has the potential to achieve a clinically significant improvement of uncorrected visual acuity. Georg Thieme Verlag KG Stuttgart · New York.
Galindo, Sara; Herreras, José M; López-Paniagua, Marina; Rey, Esther; de la Mata, Ana; Plata-Cordero, María; Calonge, Margarita; Nieto-Miguel, Teresa
Limbal stem cells are responsible for the continuous renewal of the corneal epithelium. The destruction or dysfunction of these stem cells or their niche induces limbal stem cell deficiency (LSCD) leading to visual loss, chronic pain, and inflammation of the ocular surface. To restore the ocular surface in cases of bilateral LSCD, an extraocular source of stem cells is needed to avoid dependence on allogeneic limbal stem cells that are difficult to obtain, isolate, and culture. The aim of this work was to test the tolerance and the efficacy of human adipose tissue-derived mesenchymal stem cells (hAT-MSCs) to regenerate the ocular surface in two experimental models of LSCD that closely resemble different severity grades of the human pathology. hAT-MSCs transplanted to the ocular surface of the partial and total LSCD models developed in rabbits were well tolerated, migrated to inflamed tissues, reduced inflammation, and restrained the evolution of corneal neovascularization and corneal opacity. The expression profile of the corneal epithelial cell markers CK3 and E-cadherin, and the limbal epithelial cell markers CK15 and p63 was lost in the LSCD models, but was partially recovered after hAT-MSC transplantation. For the first time, we demonstrated that hAT-MSCs improve corneal and limbal epithelial phenotypes in animal LSCD models. These results support the potential use of hAT-MSCs as a novel treatment of ocular surface failure due to LSCD. hAT-MSCs represent an available, non-immunogenic source of stem cells that may provide therapeutic benefits in addition to reduce health care expenses. Stem Cells 2017;35:2160-2174. © 2017 AlphaMed Press.
Jang, In-Keun; Ahn, Jae-Il; Shin, Jun-Seop; Kwon, Young-Sam; Ryu, Yang-Hwan; Lee, Jeong-Kyu; Park, Jung-Keug; Song, Kye-Yong; Yang, Eun-Kyung; Kim, Jae-Chan
The purpose of this article was to evaluate the graft efficacy of reconstructed corneal layer, composed of autologous corneal epithelium and fibroblasts on a lyophilized amniotic membrane (LAM), in a severely alkali-burned corneal model. After biopsy specimens were obtained from the left eyes of 24 rabbits, the corneal epithelial cells and fibroblasts were expanded in vitro and the corneal layer was reconstructed on LAM. Thirty-six eyes of rabbits underwent alkali burn (1 N NaOH, 30 s) to create a limbal deficiency and a deeply damaged corneal stroma. Four weeks later, group 1 underwent a graft of the reconstructed corneal layer composed of autologous corneal epithelium and fibroblasts on LAM. Group 2 was transplanted with a graft of the reconstructed autologous corneal epithelium, and group 3 served as a control without surgery. Wound healing and stabilization of the ocular surfaces occurred much faster in group 1 than in groups 2 and 3. The eyes in group 3 revealed typical limbal deficiencies with conjuctivalization and persistent corneal epithelial defects. However, the corneas in group 1 developed only mild peripheral neovascularization. Immunohistochemical staining in group 1 demonstrated that p63, cytokeratin 3, E-cadherin, transforming growth factor (TGF)-beta1, and collagen IV were expressed strongly in the corneal epithelium and basement membrane. On the basis of these results, transplantation of the reconstructed corneal layer, composed of autologous corneal epithelium and fibroblasts on LAM, partially accelerated the recovery of the alkali-injured rabbit ocular surface, and might be useful therapeutically for the treatment of patients with severely damaged cornea.
Filip, M; Cârstocea, B; Beşleagă, C
Corneal transplant become a surgical procedure which is performed with success in more many ophthalmological medico-surgical centers. This way it raised a fully experience concerning selection of cases and the preservation of the graft, surgical technique and the graft rejection. The authors present a general view of the problems concerning keratoplasty making a briefly summary of the indications, contraindications and prognosis of this technique, screening of donor tissue and a little larger one the surgical technique with his problems: trephining, preserving the donor tissue and placing the graft, and also the postoperative problems--suture removal, visual correction and corneal transplant rejection.
Although corneal abrasions are commonly seen in primary care settings, the primary care literature contains scant references on detecting and managing this problem. This article provides an overview of corneal abrasion assessment and treatment. Four common etiologies of abrasion are discussed: traumatic abrasion, contact lens abrasion, foreign body abrasion, and recurrent erosion. Parameters for the history and physical examination are outlined, including sections on contact lens removal, lid eversion, and fluorescein staining. Treatment regimens for each of the etiologies are discussed, with a focus on current research on using pressure eye patches as an intervention. Indications for referral to an ophthalmologist are noted.
Ondas, Osman; Keles, Sadullah
The aim of this study was to evaluate central corneal thickness in patients with atopic keratoconjunctivitis. The study was conducted in the Atatürk University School of Medicine between April 2011 and June 2013. The study group included 60 eyes of 30 patients with atopic keratoconjunctivitis. Sixty eyes of 30 healthy individuals without any ophthalmic or systemic pathology were used as a control group. The central corneal thickness was measured with ultrasonic pachymetry. In each group, all subjects included in the study had a best corrected visual acuity (BCVA) of 20/25 or better. In the study group past medical histories revealed eczema in 19 patients, asthma in 16, and atopic dermatitis in 15. During clinical examination cicatricial conjunctivitis was noted in 5 patients, giant papillae in 4, symblepharon in 2, and entropion in 2. The mean central corneal thickness was 523.45±18.03 µm in the study group (mean age: 37.05±5.7 years) and 540.30±38.91 µm in the control group (mean age: 36.55±7.1 years), and the difference was statistically significant (p<0.001). Evaluation of corneal thickness is important in situations such as corneal refractive surgery and contact lens use, and is an essential parameter in a wide range of ocular disorders, including glaucoma and keratoconus. Therefore, ophthalmologists should be aware of the low central corneal thickness in patients with atopic keratoconjunctivitis.
Lindstrom, R L
The functional status of the endothelium and sustained corneal deturgescence after corneal preservation are of great clinical importance and have been primary goals in the development of corneal storage media. In our investigational studies we have specifically addressed the improvement of the quality of donor tissue after 4 degrees C storage, the extension of corneal preservation time, the enhancement of corneal wound healing, and the reduction of the normal progressive loss of endothelial cells postkeratoplasty. Specifically we have developed in vitro HCE cell and epithelial cell culture models that can accurately reflect the response of human corneal tissue in vivo. These models have been utilized to study the effects of growth factors and medium components in relation to their biocompatibility and efficacy in the development of improved corneal preservation solutions. Our laboratory investigated in vitro conditions that allowed human corneal endothelium to shift from a nonproliferative state, in which they remain viable and metabolically active, to a proliferative, mitotically active state. Isolation techniques developed in our laboratory have enabled the establishment of primary and subsequent subcultures of human corneal endothelium that retain the attributes of native endothelium. These in vitro conditions maintain HCE cells in a proliferative state, actively undergoing mitosis. A quantitative bioassay has been developed to determine the effects of various test medium in the stimulation or inhibition of DNA synthesis. In attempting to learn more about the events that occur during in vitro endothelial cell isolation, cell reattachment, extracellular matrix interaction and migrating during subculture, SEM was done on isolated HCE cells incubated in CSM. These studies suggest that the components of the extracellular matrix modulate the growth response of HCE cells, and play a role in regulating proliferation and migration. These observations are important in
Pang, Kunpeng; Du, Liqun; Zhang, Kai; Dai, Chenyang; Ju, Chengqun; Zhu, Jing; Wu, Xinyi
The aim of this study was to construct a rabbit anterior corneal replacement for transplantation using acellular porcine corneal matrix (APCM) and rabbit epithelial or stromal cells. APCM was prepared from fresh porcine cornea treated with 0.5% (wt./vol.) sodium dodecyl sulfate (SDS) solution. The expanded stromal cells were first injected into APCM parallel to its surface and were cultured in a shaking culture system for 7 days to obtain the stromal construct. Next, corneal epithelial cells were cultured on the stromal construct surface for another 7 days to obtain rabbit anterior corneal lamella. The construct had a phenotype similar to that of normal cornea, with high expression of cytokeratin 3 in the epithelial cell layer and vimentin in the stromal cells. More importantly, the construct integrated well with the implanted host corneal tissue, and the implant cornea maintained transparency in the 6-month follow-up, although there was a slight haze in the central corneal area. The endothelium in the surgery cornea had a similar cell density and mosaic pattern with normal cornea as shown by confocal laser corneal microscopy, and the regenerated corneal epithelial cells on the implant surface showed a similar morphology to that of natural epithelial cells. These results demonstrate that the constructed anterior corneal replacement exhibits an excellent biological property for lamellar keratoplasty and might be a possible alternative to human corneal tissue in the future. PMID:27930708
Hos, Deniz; Saban, Daniel R; Bock, Felix; Regenfuss, Birgit; Onderka, Jasmine; Masli, Sharmila; Cursiefen, Claus
To analyze whether topical application of corticosteroids inhibits inflammatory corneal lymphangiogenesis and to study the potential underlying antilymphangiogenic mechanisms. Inflammatory corneal neovascularization was induced by suture placement, and the corneas were then treated with topical fluorometholone, prednisolone acetate, or dexamethasone sodium phosphate. After 1 week, the corneas were stained with lymphatic vessel endothelial hyaluronan receptor 1 for detection of pathological corneal lymphangiogenesis. The effect of these corticosteroids on macrophage recruitment was assessed via fluorescence-activated cell sorting analysis. The effect of these corticosteroids on proinflammatory cytokine expression by peritoneal exudate cells was tested via real-time polymerase chain reaction. Furthermore, the effect of steroid treatment on the proliferation of lymphatic endothelial cells was assessed via enzyme-linked immunosorbent assay. Treatment with corticosteroids resulted in a significant reduction of inflammatory corneal lymphangiogenesis. The antilymphangiogenic effect of fluorometholone was significantly weaker than that of prednisolone and dexamethasone. Corneal macrophage recruitment was also significantly inhibited by the application of topical steroids. Treatment of peritoneal exudate cells with corticosteroids led to a significant downregulation of the RNA expression levels of tumor necrosis factor and interleukin 1β. Additionally, proliferation of lymphatic endothelial cells was also inhibited. Corticosteroids are strong inhibitors of inflammatory corneal lymphangiogenesis, with significant differences between various corticosteroids in terms of their antilymphangiogenic potency. The main mechanism of the antilymphangiogenic effect seems to be through the suppression of macrophage infiltration, proinflammatory cytokine expression, and direct inhibition of proliferation of lymphatic endothelial cells. Steroids block corneal lymphangiogenesis, the main
Schultz, R O; Peters, M A; Sobocinski, K; Nassif, K; Schultz, K J
Corneal epithelial lesions can be found in approximately one-half of asymptomatic patients with diabetes mellitus. These lesions are transient and clinically resemble the keratopathy seen in staphylococcal keratoconjunctivitis. Staphylococcal organisms, however, can be isolated in equal percentages from diabetic patients without keratopathy. Diabetic peripheral neuropathy was found to be related to the presence of diabetic keratopathy after adjusting for age with analysis of covariance. The strongest predictor of both keratopathy and corneal fluorescein staining was vibration perception threshold in the toes (P less than 0.01); and the severity of keratopathy was directly related to the degree of diminution of peripheral sensation. Other predictors of keratopathy were: reduced tear breakup time (P less than 0.03), type of diabetes (P less than 0.01), and metabolic status as indicated by c-peptide fasting (P less than 0.01). No significant relationships were found between the presence of keratopathy and tear glucose levels, endothelial cell densities, corneal thickness measurements, the presence of S epidermidis, or with duration of disease. It is our conclusion that asymptomatic epithelial lesions in the nontraumatized diabetic cornea can occur as a manifestation of generalized polyneuropathy and probably represent a specific form of corneal neuropathy. Images FIGURE 1 FIGURE 2 FIGURE 3 PMID:6676964
Batawi, Hatim; Kothari, Nikisha; Camp, Andrew; Bernhard, Luis; Karp, Carol L.; Galor, Anat
Purpose We report the case of a 77-year-old man with no history of keratoconus or other ectatic disorders who presented with corneal hydrops in the setting of a corneal ulcer. The risk factors, pathogenesis and treatment options of corneal hydrops are discussed. Method This is an observational case report study. Results A 77-year-old man presented with a 1-day history of severe pain, redness, mucous discharge and photophobia in the right eye. A slit-lamp examination of the right eye showed an area of focal corneal edema and protrusion. Within the area of edema and protrusion, there was an infiltrate with an overlying epithelial defect consistent with an infectious corneal ulcer. The Seidel test showed no leakage, so a clinical diagnosis of corneal hydrops associated with nonperforated corneal ulcer was made. With appropriate antibiotic treatment, the corneal ulcer and hydrops both resolved over a 1-month period. Conclusion Corneal hydrops can occur in the setting of corneal infections. PMID:26889160
Campos-García, Manuel; Estrada-Molina, Amilcar; Díaz-Uribe, Rufino
In this work we report the design of a null screen for corneal topography. Here we assume that the corneal surface is an ellipsoid with a diameter of 12 mm and a curvature radius of 7.8 mm. To avoid the difficulties in the alignment of the test system due to the face contour (eyebrows, nose, or eyelids), we design a conical null-screen with spots (similar to ellipses) drawn on it in such a way that its image, which is formed by reflection on the test surface, becomes an exact radial array of circular spots if the surface is perfect. Additionally, we performed a numerical simulation introducing Gaussian random errors in the coordinates of the centroids of the spots on the image plane, and in the coordinates of the sources (spots on the null-screen) in order to obtain the conical null-screen that reduces the error in the evaluation of the topography.
Marcos, Susana; Kling, Sabine; Bekesi, Nandor; Dorronsoro, Carlos
The combination of air-puff systems with real-time corneal imaging (i.e. Optical Coherence Tomography (OCT), or Scheimpflug) is a promising approach to assess the dynamic biomechanical properties of the corneal tissue in vivo. In this study we present an experimental system which, together with finite element modeling, allows measurements of corneal biomechanical properties from corneal deformation imaging, both ex vivo and in vivo. A spectral OCT instrument combined with an air puff from a non-contact tonometer in a non-collinear configuration was used to image the corneal deformation over full corneal cross-sections, as well as to obtain high speed measurements of the temporal deformation of the corneal apex. Quantitative analysis allows direct extraction of several deformation parameters, such as apex indentation across time, maximal indentation depth, temporal symmetry and peak distance at maximal deformation. The potential of the technique is demonstrated and compared to air-puff imaging with Scheimpflug. Measurements ex vivo were performed on 14 freshly enucleated porcine eyes and five human donor eyes. Measurements in vivo were performed on nine human eyes. Corneal deformation was studied as a function of Intraocular Pressure (IOP, 15-45 mmHg), dehydration, changes in corneal rigidity (produced by UV corneal cross-linking, CXL), and different boundary conditions (sclera, ocular muscles). Geometrical deformation parameters were used as input for inverse finite element simulation to retrieve the corneal dynamic elastic and viscoelastic parameters. Temporal and spatial deformation profiles were very sensitive to the IOP. CXL produced a significant reduction of the cornea indentation (1.41x), and a change in the temporal symmetry of the corneal deformation profile (1.65x), indicating a change in the viscoelastic properties with treatment. Combining air-puff with dynamic imaging and finite element modeling allows characterizing the corneal biomechanics in-vivo.
Ambrósio, Jr, Renato; Correia, Fernando Faria; Lopes, Bernardo; Salomão, Marcella Q.; Luz, Allan; Dawson, Daniel G.; Elsheikh, Ahmed; Vinciguerra, Riccardo; Vinciguerra, Paolo; Roberts, Cynthia J.
Background: Ectasia development occurs due to a chronic corneal biomechanical decompensation or weakness, resulting in stromal thinning and corneal protrusion. This leads to corneal steepening, increase in astigmatism, and irregularity. In corneal refractive surgery, the detection of mild forms of ectasia pre-operatively is essential to avoid post-operative progressive ectasia, which also depends on the impact of the procedure on the cornea. Method: The advent of 3D tomography is proven as a significant advancement to further characterize corneal shape beyond front surface topography, which is still relevant. While screening tests for ectasia had been limited to corneal shape (geometry) assessment, clinical biomechanical assessment has been possible since the introduction of the Ocular Response Analyzer (Reichert Ophthalmic Instruments, Buffalo, USA) in 2005 and the Corvis ST (Oculus Optikgeräte GmbH, Wetzlar, Germany) in 2010. Direct clinical biomechanical evaluation is recognized as paramount, especially in detection of mild ectatic cases and characterization of the susceptibility for ectasia progression for any cornea. Conclusions: The purpose of this review is to describe the current state of clinical evaluation of corneal biomechanics, focusing on the most recent advances of commercially available instruments and also on future developments, such as Brillouin microscopy. PMID:28932334
Kaya, Murat; Sargin, Idris; Al-Jaf, Ivan; Erdogan, Sevil; Arslan, Gulsin
Chitin in the compound eyes of arthropods serves as a part of the visual system. The quality of chitin in such highly specialised body parts deserves more detailed examination. Chitin in the corneal (ommatidial) lenses of dragonfly (Sympetrum fonscolombii) compound eyes was isolated by using the classical chemical method. The chitin content of the corneal lenses was determined to be quite high (20.3±0.85%). The FT-IR analysis showed that corneal lens chitin was in the α-form as found in all arthropod species where mechanical strength is required. The surface morphology analysis by scanning electron microscopy revealed that the outer part of corneal lenses consisted of long chitin fibrils with regular arrays of papillary structures while the smoother inner part had concentric lamellated chitin formation with shorter chitin nanofibrils. Chitinase enzymatic digestion studies, elemental analysis results and the degree of acetylation value showed the purity of chitin samples from corneal lens. The maximum degradation temperature value of the corneal lens chitin was observed at 369.2°C. X-ray analysis revealed that corneal lens chitin has high crystallinity index; 96.4%. Identification of chitin found in ommaditia of insect compound eyes can provide insights into insect vision and chitin-based optical material design studies.
Bajwa, Preety; Nagendra, Prathima B.; Nielsen, Sarah; Sahoo, Subhransu S.; Bielanowicz, Amanda; Lombard, Janine M.; Wilkinson, Erby J.; Miller, Richard A.; Tanwar, Pradeep S.
Ovarian cancer is a disease of older women. However, the molecular mechanisms of ovarian aging and their contribution to the pathogenesis of ovarian cancer are currently unclear. mTOR signalling is a major regulator of aging as suppression of this pathway extends lifespan in model organisms. Overactive mTOR signalling is present in up to 80% of ovarian cancer samples and is associated with poor prognosis. This study examined the role of mTOR signalling in age-associated changes in ovarian surface epithelium (OSE). Histological examination of ovaries from both aged mice and women revealed OSE cell hyperplasia, papillary growth and inclusion cysts. These pathological lesions expressed bonafide markers of ovarian cancer precursor lesions, Pax8 and Stathmin 1, and were presented with elevated mTOR signalling. To understand whether overactive mTOR signalling is responsible for the development of these pathological changes, we analysed ovaries of the Pten trangenic mice and found significant reduction in OSE lesions compared to controls. Furthermore, pharmacological suppression of mTOR signalling significantly decreased OSE hyperplasia in aged mice. Treatment with mTOR inhibitors reduced human ovarian cancer cell viability, proliferation and colony forming ability. Collectively, we have established the role of mTOR signalling in age-related OSE pathologies and initiation of ovarian cancer. PMID:27036037
Hirano, Koji; Koide, Mihoko; Mizoguchi, Yoshikazu; Osakabe, Yasuhiro; Sasaki, Kaoru-Araki
Purpose Leukoplakia is the term given to a white patch or plaque that is found mainly on the oral mucus membrane. It can occasionally be seen on the corneal surface. We report our clinical and histopathological findings in a case of unilateral corneal leukoplakia. Methods A 26-year-old woman was referred to our hospital because of a white patch on her right cornea that continued to expand. She first noticed the white patch when she was 20 years old, and the white patch had expanded to cover the pupillary area affecting her vision. After plastic surgery on both eyelids for bilateral entropion to alleviate the pain caused by the eyelashes rubbing the cornea, the white corneal patch decreased in size. Because of this reduction, we performed surgery to remove the patch with microforceps under topical anesthesia. The plaque was removed easily and completely, and submitted for histopathological examination. Results Histopathological examination showed that the specimen had characteristics of epidermis with a basal cell layer, spinous cell layer, granular cell layer, and horny layer with hyperkeratosis. She was diagnosed with leukoplakia of the corneal surface. The basic structure of the squamous cell layer was preserved, and there were no signs of metaplasia. Six months after the removal of the leukoplakia, no recurrence was seen and her corrected decimal visual acuity recovered to 1.0. Conclusion Our case of unilateral corneal leukoplakia without limbal involvement was most likely caused by chronic irritation of the cornea by the eyelashes. Although it was totally removed with good recovery of vision, we continue to follow the patient because of the potential of malignant transformation. PMID:26056494
Naik, M N; Gangopadhyay, N; Fernandes, M; Murthy, R; Honavar, S G
To evaluate the effectiveness of anterior chemodenervation of levator palpebrae superioris with Botulinum toxin type A (Botox) to induce temporary ptosis for corneal protection, and assess the incidence of superior rectus underaction. Prospective interventional case series. Patients with ocular surface pathology requiring temporary tarsorrhaphy underwent transcutaneous anterior chemodenervation of levator palpebrae superioris with Botox. The onset and duration of ptosis, corneal healing, and superior rectus underaction was evaluated. Ten eyes of 10 patients underwent transcutaneous anterior chemodenervation of levator muscle. Five patients had Bells palsy with exposure keratopathy, four patients had persistent epithelial defect, and one had neurotrophic ulcer. The median age at presentation was 30 years. Median dose of Botulinum toxin injection was 12.5 U (range 10-15 U). The mean palpebral fissure height of 9 mm (SD+/-2.1 mm) before injection, reduced to 2.8 mm (SD+/-1.9 mm) at 1-week post-injection. More than 50% reduction in palpebral fissure height was seen in nine out of 10 eyes (90%, 95% CI 71.4-100%) at 1 week, seven of nine eyes (77.8%, 95% CI 50.6-100%) at 2 weeks, and two of nine eyes (22.2%, 95% CI 0-49.4%) at 4 weeks, and returned to pretreatment level after mean duration of 9.2 weeks (range 5-16 weeks). Superior rectus underaction was not noted in any of the patient (95% CI 0-30%). Corneal pathology improved in all cases. Anterior chemodenervation of levator palpebrae superioris with Botulinum toxin type A (Botox) induces significant temporary ptosis and aids in corneal healing. Anterior placement of the toxin injection may avoid superior rectus underaction.
Nemeth, Gabor; Szalai, Eszter; Hassan, Ziad; Lipecz, Agnes; Flasko, Zsuzsa; Modis, Laszlo
AIM To analyze the correlations between ocular biomechanical and biometric data of the eye, measured by Scheimpflug-based devices on healthy subjects. METHODS Three consecutive measurements were carried out using the corneal visualization Scheimpflug technology (CorVis ST) device on healthy eyes and the 10 device-specific parameters were recorded. Pentacam HR-derived parameters (corneal curvature radii on the anterior and posterior surfaces; apical pachymetry; corneal volume; corneal aberration data; depth, volume and angle of the anterior chamber) and axial length (AL) from IOLMaster were correlated with the 10 specific CorVis ST parameters. RESULTS Measurements were conducted in 43 eyes of 43 volunteers (age 61.24±15.72y). The 10 specific CorVis ST data showed significant relationships with corneal curvature radii both on the anterior and posterior surface, pachymetric data, root mean square (RMS) data of lower-order aberrations, and posterior RMS of higher-order aberrations and spherical aberration of the posterior cornea. Anterior chamber depth showed a significant relationship, but there were no significant correlations between corneal volume, anterior chamber volume, mean chamber angle or AL and the 10 specific CorVis ST parameters. CONCLUSIONS CorVis ST-generated parameters are influenced by corneal curvature radii, some corneal RMS data, but corneal volume, anterior chamber volume, chamber angle and AL have no correlation with the biomechanical parameters. The parameters measured by CorVis ST seem to refer mostly to corneal properties of the eye. PMID:28251079
Hos, Deniz; Bukowiecki, Anne; Horstmann, Jens; Bock, Felix; Bucher, Franziska; Heindl, Ludwig M; Siebelmann, Sebastian; Steven, Philipp; Dana, Reza; Eming, Sabine A; Cursiefen, Claus
Lymphangiogenesis is essential for fluid homeostasis in vascularized tissues. In the normally avascular cornea, however, pathological lymphangiogenesis mediates diseases like corneal transplant rejection, dry eye disease, and allergy. So far, a physiological role for lymphangiogenesis in a primarily avascular site such as the cornea has not been described. Using a mouse model of perforating corneal injury that causes acute and severe fluid accumulation in the cornea, we show that lymphatics transiently and selectively invade the cornea and regulate the resolution of corneal edema. Pharmacological blockade of lymphangiogenesis via VEGFR-3 inhibition results in increased corneal thickness due to delayed drainage of corneal edema and a trend towards prolonged corneal opacification. Notably, lymphatics are also detectable in the cornea of a patient with acute edema due to spontaneous Descemet´s (basement) membrane rupture in keratoconus, mimicking this animal model and highlighting the clinical relevance of lymphangiogenesis in corneal fluid homeostasis. Together, our findings provide evidence that lymphangiogenesis plays an unexpectedly beneficial role in the regulation of corneal edema and transparency. This might open new treatment options in blinding diseases associated with corneal edema and transparency loss. Furthermore, we demonstrate for the first time that physiological lymphangiogenesis also occurs in primarily avascular sites.
Bregnhøj, Jesper F; Mataji, Pourang; Naeser, Kristian
To evaluate the correlation between refractive astigmatism (RA) and anterior corneal astigmatism (ACA), and determine the internal astigmatism (IA) in 184 pseudophakic eyes. The study was a prospective non-masked single-centre study. Patients were examined 8 weeks after phacoemulsification with implantation of aspheric one-piece monofocal IOLs. Examination included autokeratometry and subjective refraction. All refractive data were converted to the corneal plane. The corneal refractive index, taken to be 1.376, was used to estimate the ACA. All astigmatisms were converted to net curvital and net torsional powers with the steeper corneal plane as the reference meridian. Curvital power is the force acting along a given meridian, and torsion is the power twisting the astigmatic direction out of that plane. The internal astigmatism (IA) was calculated as the difference between RA and ACA. For curvital powers, the refractive astigmatism (KP(Φ)RA ) could be described as a function of anterior corneal astigmatic magnitude (KP(Φ)ACA ) and direction α by the multiple linear regression equation: KP(Φ)RA = -0.09 + 0.61*KP(Φ)ACA + 0.33*cos2α, (r(2) = 0.59, p < 0.0001). The average internal astigmatism amounted to 0.47 D inclined 92° relative to the steeper anterior corneal meridian. The magnitude of internal astigmatism depended on the angle α of the steeper anterior corneal meridian, averaging 0.86 D at 91° for with-the-rule, 0.37 D at 95° for oblique and 0.17 D at 97° for against-the-rule corneal astigmatisms. The internal astigmatism varies as a function of the direction of the anterior steeper corneal meridian. In patient candidates to surgical correction of astigmatism, measuring only the curvature of the anterior corneal surface and neglecting that of the posterior corneal surface can lead to inaccurate evaluation of total corneal astigmatism. © 2014 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.
Cejková, Jitka; Cejka, Cestmír; Luyckx, Jacques
The UVB-irradiated cornea is damaged by oxidative stress. Toxic oxygen products induced by UVB radiation in the cornea are insufficiently removed by antioxidants, whose numbers decrease with increasing UVB irradiation. In addition, the UVB-irradiated cornea suffers from hypoxic conditions because damaged corneal cells cannot utilize oxygen normally, although the supply of oxygen to the cornea is unchanged (normal). This contributes to attenuated re-epithelialization, corneal neovascularization and apoptotic cell death. Our previous publications reported that trehalose applied on the corneal surface during irradiation significantly suppressed UVB-induced corneal oxidative damage. The results of this study provide for the first time important evidence that trehalose applied on the surface of corneas for two weeks following repeated UVB irradiation (312 nm, daily dose 0.5 J/cm2) accelerated corneal healing, restored corneal transparency and suppressed corneal neovascularization. Compared to buffered saline treatment, following which caspase-3, nitrotyrosine, malondialdehyde and urokinase-type plasminogen activator were still strongly expressed in the corneal epithelium two weeks after irradiation and corneal neovascularization was evident, apoptotic cell death was already significantly reduced after one week of trehalose application. The expression of other markers of injury returned to normal levels during two weeks of trehalose treatment. In conclusion, our results show that trehalose accelerated healing of the UVB irradiated cornea, very probably via suppression of hypoxia-response injury. In addition, immunohistochemical results on corneal cryostat sections corresponded with those obtained using corneal impression cytologies, thus confirming that corneal impression cytologies are useful for diagnostic purposes.
Shin, Jun Geun; Lee, Byeong Ha; Eom, Tae Joong; Hwang, Ho Sik
We have imaged human corneal nerve bundles by using real-time Fourier-domain OCT (FD-OCT). Corneal nerves contribute to the maintenance of healthy ocular surface owing to their trophic influences on the corneal epithelium. The FD-OCT system was based on a swept laser of a 50 kHz sweeping rate and 1.31 μm center wavelength. At the area including sclera, limbus, and cornea, we could successfully get the in-vivo tomograms of the corneal nerve bundles. The scan range was 5 x 5mm. In this study, the A-scan images in each B-scan were realigned to have a flat air-surface boundary in the final B-scan image. With this effort, we could align corneal nerve bundle in a same depth and get the 3D image showing the branched and threadlike corneal nerve bundles.
Kahn, Fredrik; Mörgelin, Matthias; Shannon, Oonagh; Norrby-Teglund, Anna; Herwald, Heiko; Olin, Anders I.; Björck, Lars
Streptococcal toxic shock syndrome (STSS) caused by Streptococcus pyogenes is a clinical condition with a high mortality rate despite modern intensive care. A key feature of STSS is excessive plasma leakage leading to hypovolemic hypotension, disturbed microcirculation and multiorgan failure. Previous work has identified a virulence mechanism in STSS where M1 protein of S. pyogenes forms complexes with fibrinogen that activate neutrophils to release heparin-binding protein (HBP), an inducer of vascular leakage. Here, we report a marked inter-individual difference in the response to M1 protein–induced HBP release, a difference found to be related to IgG antibodies directed against the central region of the M1 protein. To elicit massive HBP release, such antibodies need to be part of the M1 protein–fibrinogen complexes. The data add a novel aspect to bacterial pathogenesis where antibodies contribute to the severity of disease by promoting a pathologic inflammatory response. PMID:18787689
Wacker, Katrin; McLaren, Jay W.; Kane, Katrina M.; Baratz, Keith H.; Patel, Sanjay V.
Purpose To assess corneal hydration control across a range of severity of Fuchs' endothelial corneal dystrophy (FECD) by measuring the percent recovery per hour (PRPH) of central corneal thickness after swelling the cornea and to determine its association with corneal morphologic parameters. Methods Twenty-three corneas of 23 phakic FECD patients and 8 corneas of 8 healthy control participants devoid of guttae were graded (modified Krachmer scale). Effective endothelial cell density (ECDe) was determined from the area of guttae and local cell density in confocal microscopy images. Steady-state corneal thickness (CTss) and standardized central corneal backscatter were derived from Scheimpflug images. Corneal swelling was induced by wearing a low-oxygen transmissible contact lens for 2 hours in the morning. De-swelling was measured over 5 hours after lens removal or until corneal thickness returned to CTss. Percent recovery per hour was 100 × (1 – e−k), where k was determined from CT(t) = (de−kt) + CTss, and where d was the initial change from CTss. Results After contact lens wear, corneas swelled by 9% (95% CI 9–10). Percent recovery per hour was 49%/h (95% CI 41–57) in controls and 37%/h in advanced FECD (95% CI 29–43, P = 0.028). Low PRPH was associated with disease severity, low ECDe, and increased anterior and posterior corneal backscatter. Anterior backscatter was associated with PRPH in a multivariable model (R2 = 0.44). Conclusions Corneal hydration control is impaired in advanced FECD and is inversely related to anterior corneal backscatter. Anterior corneal backscatter might serve as an indicator of impaired endothelium in FECD. PMID:27661858
Haq, Syed Nadeem Ul; Ayub, Zeeshan; Ahmed, Azeema
To determine the best method of identifying core tonsillar flora. Quasi-experimental study. ENT Department, Combined Military Hospital, Lahore, from September 2013 to October 2015. Eighty-seven patients of recurrent tonsillitis undergoing tonsillectomy were included. All the patients, after being anaesthetised, had surface swabs taken from the tonsillar surface followed by tonsillar aspiration with a 5cc syringe. Following tonsillectomy, the tonsils were sent for culture of core flora. All three specimens from each patient were cultured according to established criteria. The patient population had 33 (37%) female and 54 (62%) male patients. Flora of 12 (13.8%) surface swabs and 68 (78.2%) tonsillar aspirates matched the flora cultured from core of the tonsils. Chi-square test showed this difference to be significant (p-value <0.001). Tonsillar aspiration gave a much more realistic picture of the tonsillar core flora as compared to surface swabs.
Cuna, W R; Cuna, C R
Human Chagas' disease, caused by the protozoan Trypanosoma cruzi, is associated with pathological processes whose mechanisms are not known. To address this question, T cell lines were developed from chronic chagasic patients peripheral blood mononuclear cells (PBMC) and cloned. These T cell clones (TCC) were analyzed phenotypically with monoclonal antibodies by the use of a fluorescence microscope. The surface phenotype of the TCC from the asymptomatic patient were predominantly CD4 positive (86%). On the contrary, the surface phenotype CD8 was predominant in the TCC from the patients suffering from cardiomegaly with right bundle branch block (83%), bradycardia with megacolon (75%) and bradycardia (75%). Future studies will be developed in order to identify the antigens eliciting these T cell subpopulations.
Campos-García, Manuel; Cossio-Guerrero, Cesar; Huerta-Carranza, Oliver; Moreno-Oliva, Víctor I.
In this work we report the design of a null-screen for corneal topography. To avoid the difficulties in the alignment of the test system due to the face contour (eyebrows, nose, or eyelids), we design a conical null-screen with a novel radial points distribution drawn on it in such a way that its image, which is formed by reflection on the test surface, becomes an exact array of circular spots if the surface is perfect. Additionally, an algorithm to compute the sagittal and meridional radii of curvature for the corneal surface is presented. The sagittal radius is obtained from the surface normal, and the meridional radius is calculated from a function fitted to the derivative of the sagittal curvature by using the surfacenormals raw data. Experimental results for the testing a calibration spherical surface are shown. Also, we perform some corneal topography measurements.
We evaluated the refractive consequences of corneal transplants using a biomechanical model with homogeneous and inhomogeneous Young's modulus distributions within the cornea, taking into account ablation of some stromal tissue. A FEM model was used to simulate corneal transplants in diseased cornea. The diseased cornea was modeled as an axisymmetric structure taking into account a nonlinearly elastic, isotropic formulation. The model simulating the penetrating keratoplasty procedure gives more change in the postoperative corneal curvature when compared to the models simulating the anterior and posterior lamellar graft procedures. When a lenticle shaped tissue was ablated in the graft during the anterior and posterior keratoplasty, the models provided an additional correction of about -3.85 and -4.45 diopters, respectively. Despite the controversy around the corneal thinning disorders treatment with volume removal procedures, results indicate that significant changes in corneal refractive power could be introduced by a corneal transplantation combined with myopic laser ablation.
Kalteniece, Alise; Ferdousi, Maryam; Adam, Safwaan; Schofield, Jonathan; Azmi, Shazli; Petropoulos, Ioannis; Soran, Handrean; Malik, Rayaz A
To assess the effect of applying a protocol for image selection and the number of images required for adequate quantification of corneal nerve pathology using in vivo corneal confocal microscopy (IVCCM). IVCCM was performed in 35 participants by a single examiner. For each participant, 4 observers used a standardized protocol to select 6 central corneal nerve images to assess the inter-observer variability. Furthermore, images were selected by a single observer on two occasions to assess intra-observer variability and the effect of sample size was assessed by comparing 6 with 12 images. Corneal nerve fiber density (CNFD), branch density (CNBD) and length (CNFL) were quantified using fully automated software. The data were compared using the intra class correlation coefficient (ICC) and Bland-Altman agreement plots for all experiments. The ICC values for CNFD, CNBD and CNFL were 0.93 (P<0.0001), 0.96 (P<0.0001) and 0.95 (P<0.0001) for inter-observer variability and 0.95 (P<0.0001), 0.97 (P<0.001) and 0.97 (P<0.0001) for intra-observer variability. For sample size variability, ICC values were 0.94 (P<0.0001), 0.95 (P<0.0001), and 0.96 (P<0.0001) for CNFD, CNBD and CNFL. Bland-Altman plots showed excellent agreement for all parameters. This study shows that implementing a standardized protocol to select IVCCM images results in high intra and inter-observer reproducibility for all corneal nerve parameters and 6 images are adequate for analysis. IVCCM could therefore be deployed in large multicenter clinical trials with confidence.
Pole, Cameron; Sise, Adam; Joag, Madhura; Galor, Anat; Bermudez-Magner, Jose Antonio; Dubovy, Sander; Karp, Carol L.
Purpose To describe a case of Lisch epithelial corneal dystrophy (LECD) and present its unique characteristics on high-resolution optical coherence tomography (HR-OCT). Methods A 78-year-old man with whorled corneal epithelial opacities in the right eye was referred for evaluation of ocular surface squamous neoplasia. Clinical evaluation, photos, and HR-OCT images of involved cornea were obtained and scrapings of the affected cornea were sent for histopathologic analysis. Results Clinically the patient presented with a opalescent whirling epithelium in a linear pattern encroaching on the visual axis. HR-OCT showed normal thickness epithelial hyperreflectivity of involved cornea without stromal involvement, along with sharply demarcated borders of unaffected tissue. Histopathologic findings demonstrated vacuolated PAS-positive cells throughout the epithelial layers consistent with LECD. Conclusions HR-OCT was able to provide useful information to rule out ocular surface squamous neoplasia, and confirm the clinical impression of LECD at the time of clinical examination. HR-OCT shows promise as an adjunctive diagnostic tool for ocular surface lesions and pathologies. PMID:26764880
Wagner, Joerg; Goldblum, David; Cattin, Philippe C
Corneal topography allows the assessment of the cornea's refractive power which is crucial for diagnostics and surgical planning. The use of optical coherence tomography (OCT) for corneal topography is still limited. One limitation is the susceptibility to disturbances like blinking of the eye. This can result in partially corrupted scans that cannot be evaluated using common methods. We present a new scanning method for reliable corneal topography from partial scans. Based on the golden angle, the method features a balanced scan point distribution which refines over measurement time and remains balanced when part of the scan is removed. The performance of the method is assessed numerically and by measurements of test surfaces. The results confirm that the method enables numerically well-conditioned and reliable corneal topography from partially corrupted scans and reduces the need for repeated measurements in case of abrupt disturbances.
Mohan, Rajiv R; Rodier, Jason T; Sharma, Ajay
Corneal blindness is the third leading cause of blindness worldwide. Gene therapy is an emerging technology for corneal blindness due to the accessibility and immune-privileged nature of the cornea, ease of vector administration and visual monitoring, and ability to perform frequent noninvasive corneal assessment. Vision restoration by gene therapy is contingent upon vector and mode of therapeutic gene introduction into targeted cells/tissues. Numerous efficacious vectors, delivery techniques, and approaches have evolved in the last decade for developing gene-based interventions for corneal diseases. Maximizing the potential benefits of gene therapy requires efficient and sustained therapeutic gene expression in target cells, low toxicity, and a high safety profile. This review describes the basic science associated with many gene therapy vectors and the present progress of gene therapy carried out for various ocular surface disorders and diseases.
Mohan, Rajiv R.; Rodier, Jason T.; Sharma, Ajay
Corneal blindness is the third leading cause of blindness worldwide. Gene therapy is an emerging technology for corneal blindness due to the accessibility and immune-privileged nature of the cornea, ease of vector administration and visual monitoring, and ability to perform frequent noninvasive corneal assessment. Vision restoration by gene therapy is contingent upon vector and mode of therapeutic gene introduction into targeted cells/tissues. Numerous efficacious vectors, delivery techniques, and approaches have evolved in last decade for developing gene-based interventions for corneal diseases. Maximizing the potential benefits of gene therapy requires efficient and sustained therapeutic gene expression in target cells, low toxicity, and a high safety profile. This review describes the basic science associated with many gene therapy vectors and the present progress of gene therapy carried out for various ocular surface disorders and diseases. PMID:23838017
Del Turco, Claudia; Pierro, Luisa; Querques, Giuseppe; Gagliardi, Marco; Corvi, Federico; Manitto, Maria Pia; Bandello, Francesco M
To describe the previously unreported concomitance of 2 uncommon ocular conditions: posterior polymorphous corneal dystrophy (PPCD) and large colloid drusen (LCD). A 45-year-old woman underwent a complete ophthalmologic examination with slit-lamp biomicroscopy and blue fundus autofluorescence with spectral-domain optical coherence tomography, as well as complete systemic examination and renal function investigation. On slit-lamp biomicroscopy, a corneal lesion located at Descemet membrane was observed in the right eye. The clinical features of deep posterior stromal-endothelial linear bands with vesicles and irregular opacities of posterior corneal surface were consistent with the diagnosis of PPCD. Fundus biomicroscopy and blue fundus autofluorescence showed LCD. We report the unusual coexistence of PPCD and LCD in a young, healthy subject. Posterior polymorphous corneal dystrophy and LCD share morphologic similarities and dysfunctions of collagen architecture in the basement membrane layer, which suggests a possible common pathogenic pathway.
Wagner, Joerg; Goldblum, David; Cattin, Philippe C.
Corneal topography allows the assessment of the cornea’s refractive power which is crucial for diagnostics and surgical planning. The use of optical coherence tomography (OCT) for corneal topography is still limited. One limitation is the susceptibility to disturbances like blinking of the eye. This can result in partially corrupted scans that cannot be evaluated using common methods. We present a new scanning method for reliable corneal topography from partial scans. Based on the golden angle, the method features a balanced scan point distribution which refines over measurement time and remains balanced when part of the scan is removed. The performance of the method is assessed numerically and by measurements of test surfaces. The results confirm that the method enables numerically well-conditioned and reliable corneal topography from partially corrupted scans and reduces the need for repeated measurements in case of abrupt disturbances. PMID:28270961
Armitage, W John
Currently, cryopreservation is the only method that offers the prospect of truly long-term storage of living cells and tissues. Despite some successful cryopreserved corneal grafts, freezing has been shown to damage the endothelium. When isolated cells are frozen, there are two principal mechanisms of damage: intracellular freezing, which occurs at high cooling rates, and solution effect injury at low cooling rates. When tissues are frozen, there are additional factors that appear to render cells more susceptible to intracellular freezing. Lower cooling rates appear to overcome this when freezing cornea. Vitrification is a way of achieving ice-free cryopreservation, but it also poses considerable challenges owing to the very high solute concentrations required to achieve vitrification at practicable cooling rates. Encouraging results have also been reported for cornea frozen using non-permeating cryoprotectants, which could lead to simpler methods of corneal cryopreservation.
Morii, Tomoya; Sumioka, Takayoshi; Izutani-Kitano, Ai; Takada, Yukihisa; Okada, Yuka; Kao, Winston W-Y; Saika, Shizuya
Background. Epithelial dysplasia is categorized as conjunctival/corneal intraepithelial neoplasia which is a precancerous lesion. The lesion is usually developed at the limbal region and grows towards central cornea in association with neovascularization into the lesion. Here, we report a case of isolated nonvascularized corneal epithelial dysplasia surrounded by normal corneal epithelium with immune histochemical finding of ocular surface tissues cytokeratins, for example, keratin 13 and keratin 12. Case Presentation. A 76-year-old man consulted us for visual disturbance with localized opacification of the corneal epithelium in his left eye. His visual acuity was 20/20 and 20/200 in his right and left eye, respectively. Slit lamp examination showed a whitish plaque-like lesion at the center of his left corneal epithelium. No vascular invasion to the lesion was found. The lesion was surgically removed and subjected to histopathological examination and diagnosed as epithelial dysplasia. Amyloidosis was excluded by direct fast scarlet 4BS (DFS) staining. Immunohistochemistry showed that the dysplastic epithelial cells express keratin 13 and vimentin, but not keratin 12, indicating that the neoplastic epithelial cells lacked corneal-type epithelium differentiation. Conclusions. The lesion was diagnosed as nonvascularized epithelial dysplasia of ocular surface. Etiology of the lesion is not known.
Sharma, S L; Bajaj, R; Sharma, R
510 cases of corneal ulceration were studied for the presence of fungus as a causative organism. Fungus was found in 87 (17.5%) most common fungus found was aspergillus. Mucor was found in 16 cases (18.1%) which is higher than earlier reports. History of trauma specially with vegetative matter and the application of steriods for one purpose or the other is a factor of importance as noted in this study.
Lee, Hun; Kim, Tae-Im; Kim, Eung Kweon
Corneal astigmatism is a common refractive error observed in a significant percentage of cataract patients. Accurate measurements of the preexisting corneal astigmatism are essential in order to achieve the desired refractive outcome after toric intraocular lens (IOL) implantation. This article presents a comprehensive review of recent published literatures on methods for measuring preoperative corneal astigmatism for toric IOL implantation. A variety of instruments has been introduced and used to measure the magnitude and meridian of corneal astigmatism during preoperative assessments of cataract patients. Instruments that consider both the anterior and posterior corneal surfaces as critical factors for measuring total corneal astigmatism are expected to provide better accuracy. Although these instruments facilitate improved evaluations of corneal astigmatism and have helped minimize postoperative residual astigmatism, a perfect method to analyze preoperative corneal astigmatism has not yet been established. Perfect correction of astigmatism after toric IOL implantation by using accurate corneal astigmatism values is the goal of this surgical procedure. To achieve this, correct and precise measurements of corneal astigmatism to determine the magnitude and meridian should be obtained.
Mandathara, Preeji S; Stapleton, Fiona J; Kokkinakis, Jim; Willcox, Mark D P
To evaluate corneal sensitivity and its association with other clinical parameters in keratoconus. Twenty-four subjects with keratoconus aged between 18 and 65 years were recruited in this cross-sectional study. Ocular symptoms, corneal topography, tear variables such as tear osmolarity, volume and lower tear meniscus height, ocular surface staining, central sensitivity threshold (CST), and corneal subepithelial nerve mapping were obtained. Association between central CST and other clinical variables was examined using the Spearman correlation coefficient. Partial correlation was performed to control for effects of confounding factors. Data from the most severe eye of each subject were included in analyses. Based on the maximum simulated keratometry (Kmax) reading, subjects were graded as having mild (N = 11; K max ≤ 52 D) or severe (N = 13; K max > 52 D) keratoconus. Central corneal sensitivity was lower (ie, increased CST) in the severe keratoconus group compared with that in the mild keratoconus group (median, interquartile range: 1.09; 0.60-19.66 vs. 0.51; 0.39-1.51 g/mm, P = 0.035). In bivariate correlations, reduced corneal sensitivity in keratoconus was associated with age (ρ = 0.42, P = 0.040), disease duration (ρ = 0.49, P = 0.015) and severity (ρ = 0.44; P = 0.032), lower central nerve fiber density (ρ = -0.68, P = 0.014), contact lens wear (ρ = 0.44; P = 0.025), and contact lens tolerance (ρ = 0.46; P = 0.033). After adjusting for contact lens wear, reduced corneal sensitivity was negatively associated with ocular symptoms (ρ = -0.426, P = 0.048) and pain sensitivity (ρ = -0.423, P = 0.045) and positively associated with corneal staining (ρ = 0.52, P = 0.011). Altered corneal sensitivity in keratoconus affected ocular symptoms and ocular surface health, which may have significant impact on the success of management options for keratoconus.
Rydström, Elin; Westin, Oscar; Koskela, Timo; Behndig, Anders
To assess the anterior, posterior and total corneal spherical and astigmatic powers in patients undergoing refractive lens exchange (RLE) surgery. In 402 consecutive patients planned for RLE at Koskelas Eye Clinic, Luleå, Sweden, right eye data from pre- and postoperative subjective refraction, preoperative IOLMaster(®) biometry and Pentacam HR(®) measurements were collected. Postoperative Pentacam HR(®) data were collected for 54 of the patients. The spherical and astigmatic powers of the anterior and posterior corneal surfaces and for the total cornea were assessed and compared, and surgically, induced astigmatism was calculated using vector analysis. The spherical power of the anterior corneal surface was 48.18 ± 1.69D with an astigmatic power of 0.83 ± 0.54D. The corresponding values for the posterior surface were -6.05 ± 2,52D and 0.26 ± 0.15D, respectively. The total corneal spherical power calculated with ray tracing was 42.47 ± 2.89D with a 0.72 ± 0.48D astigmatic power, and the corresponding figures obtained by estimating the posterior corneal surface were 43.25 ± 1.51D (p < 0.001) with a 0.75 ± 0.49D astigmatic power (p = 0.003). In eyes with anterior astigmatism with-the-rule, the total corneal astigmatism is overestimated if the posterior corneal surface is estimated; in eyes, with against-the-rule astigmatism it is underestimated. Had the posterior corneal surface been measured in this material, 14.7% of the patients would have received a spheric instead of a toric IOL, or vice versa. Estimating the posterior corneal surface in RLE patients leads to systematic measurement errors that can be reduced by measuring the posterior surface. Such an approach can potentially increase the refractive outcome accuracy in RLE surgery. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.
Hegarty, Deborah M; Tonsfeldt, Karen; Hermes, Sam M; Helfand, Helen; Aicher, Sue A
Trigeminal afferents convey nociceptive information from the corneal surface of the eye to the trigeminal subnucleus caudalis (Vc). Trigeminal afferents, like other nociceptors, are thought to use glutamate and neuropeptides as neurotransmitters. The current studies examined whether corneal afferents contain both neuropeptides and vesicular glutamate transporters. Corneal afferents to the Vc were identified by using cholera toxin B (CTb). Corneal afferents project in two clusters to the rostral and caudal borders of the Vc, regions that contain functionally distinct nociceptive neurons. Thus, corneal afferents projecting to these two regions were examined separately. Dual immunocytochemical studies combined CTb with either calcitonin gene-related peptide (CGRP), substance P (SP), vesicular glutamate transporter 1 (VGluT1), or VGluT2. Corneal afferents were more likely to contain CGRP than SP, and corneal afferents projecting to the rostral region were more likely to contain CGRP than afferents projecting caudally. Overall, corneal afferents were equally likely to contain VGluT1 or VGluT2. Together, 61% of corneal afferents contained either VGluT1 or VGluT2, suggesting that some afferents lack a VGluT. Caudal corneal afferents were more likely to contain VGluT2 than VGluT1, whereas rostral corneal afferents were more likely to contain VGluT1 than VGluT2. Triple-labeling studies combining CTb, CGRP, and VGluT2 showed that very few corneal afferents contain both CGRP and VGluT2, caudally (1%) and rostrally (2%). These results suggest that most corneal afferents contain a peptide or a VGluT, but rarely both. Our results are consistent with a growing literature suggesting that glutamatergic and peptidergic sensory afferents may be distinct populations.
Kashima, Tomoyuki; Akiyama, Hideo; Miura, Fumihide; Kishi, Shoji
Rebamipide is an antiulcer agent used to treat gastric ulcer and gastritis. Biological effects of rebamipide include cytoprotection, wound healing, and anti-inflammatory properties that are known to be universal for a variety of tissues in addition to gastrointestinal mucosa. The therapeutic effects of rebamipide eye drops are due to its ability to increase corneal and conjunctival mucin-like substances and improve corneal and conjunctival injury in vivo. In this paper, we report a case of Sjögren's syndrome with complete disappearance of corneal erosion after administration of rebamipide eye drops. This was observed even though corneal erosion had not improved for 6 months after punctal occlusion surgery. The patient was a 33-year-old female, diagnosed with Sjögren's syndrome by a salivary gland biopsy. The corneal and conjunctival surfaces were filled with dense erosions, which did not improve with topical drugs. Punctal plugs were applied several times; however, the plugs were repeatedly shed. All four puncta of both eyelids were surgically occluded, and both corneal and conjunctival erosion was clearly improved. However, the erosion in the inferior cornea of both eyes had not improved for 6 months after surgery. We used the newly approved topical rebamipide for treatment of this patient. The corneal erosion gradually improved and completely disappeared 4 weeks after administration of the drug. Dry eye sensation disappeared at the same time. Both membrane-associated mucin and secreted mucin in the ocular surface are thought to be essential for maintenance of the tear film. Induction of mucin from ocular surface epithelium could be an effective treatment in cases of dry eye caused by mucin deficiency. Through its various mechanisms, rebamipide improves ocular surface conditions. To our knowledge, this is the first clinical case report using rebamipide ophthalmic solution. This drug may provide a novel approach to treat drying diseases of the eye.
Chen, Joseph J.; Rao, Kavita; Pflugfelder, Stephen C.
Purpose To compare the appearance of the superficial corneal epithelium in patients with dysfunctional tear syndrome (DTS) and an asymptomatic control group using laser scanning confocal microscopy and determine the correlations between confocal microscopic findings and clinical severity parameters. Design Prospective case control study. Methods Thirty one patients with newly diagnosed DTS and 21 asymptomatic control subjects were evaluated for this study. Subjects with DTS were classified into four levels of clinical severity (DTS 1–4) based on the Delphi dry eye panel report criteria. The Heidelberg Retina Tomograph 2 Rostock Cornea Module (HRT2-RCM) laser scanning confocal microscope was used to image the superficial corneal epithelium. Areas of single or multiple opaque superficial epithelial cells were measured as a percentage of the 400 × 400sq μm field area in four randomly selected confocal images from each eye. Spearman correlations between the confocal findings and severity of symptoms, visual acuity and ocular surface signs were calculated. Results The mean area of opaque superficial corneal epithelial cells was significantly greater in DTS patients than normal subjects (p<0.0001). Significant differences were observed between the DTS severity groups and the control group (p<0.001), except for the DTS 1 group. The area of opaque cells significantly increased with level of clinical severity. The confocal findings showed significant correlation with clinical severity parameters, including blurred vision symptoms (r = 0.86, p = 0.0001), best corrected visual acuity (BCVA) (Spearman r = 0.4, p= 0.03), conjunctival lissamine green staining scores (Spearman r= 0.4, p =0.026), corneal fluorescein staining scores (Spearman r= 0.5, p =0.002) and videokeratoscopic surface regularity index (Spearman r = 0.5, p =0.02). Conclusion Morphological changes in the superficial corneal epithelium of DTS patients detected by laser scanning confocal microscopy correlates
Spurr-Michaud, Sandra J; Gipson, Ilene K
The surface of the eye is exposed to the outside world and is, thus, subject to surface abrasion, infections, and drying, cicatrizing diseases. Availability of in vitro methods for culture of the human corneal and conjunctival epithelia, which cover the ocular surface, is therefore important in understanding the biology of these epithelia and their response to disease/infections, as well as for providing human-relevant models for preclinical testing of potential therapeutic agents. The ensuing chapter describes several methods for primary culture of both corneal and conjunctival epithelia and culture of immortalized cell lines, and methods employed to induce differentiation in the cultured epithelia.
A newly-developed macroscope was applied to observe the healing process of corneal epithelial wound in vivo. After removing epithelium of the central cornea, the changes of the corneal surface were observed with the macroscope and the findings were compared with histological examinations. At 12 hours after abrasion, areas unstained with Richardson's staining (R staining) appeared. In the histological section, a single layer of regenerating epithelial cells covered the same area. At 24 and 36 hours after abrasion, the epithelial defects became smaller but surrounding epithelium was rough and showed dot-like staining with R solution. By 2 days, the epithelial defects disappeared. On macroscopic observation, the central corneal surface showed a pavement-like appearance. Histology revealed that the regenerating epithelium still consisted of one or two layers. At 3 days, dot-like stainings were present only in the center and the corneal surface appeared considerably smooth. Histology also showed that regenerating epithelium became columnar and multilayered, thereby suggesting stratification. By 7 days, the abraded corneal surface had recovered its smooth appearance. Histologic sections also demonstrated that the epithelium had regained its normal structure. Thus, using this macroscope, findings suggesting the process of epithelial migration and proliferation could be observed.
Hama, Susumu; Itakura, Shoko; Nakai, Mayumi; Nakayama, Kayoko; Morimoto, Satoshi; Suzuki, Satoko; Kogure, Kentaro
Modification with polyethylene glycol (PEG) is currently considered an important strategy for anti-cancer drug delivery, because PEGylated-nanoparticles would be effectively delivered to tumor tissue by enhanced permeation and retention effects. However, PEGylation suppresses the cellular uptake of nanoparticles (NPs) to target cells (known as the PEG dilemma). Here, we propose a novel strategy, namely conferring a pathological environment-sensitive property of nanoparticles for overcoming the PEG dilemma. Specifically, although nanoparticles have an overall negative surface charge to avoid interactions with biogenic substances in blood circulation, inversion of surface charge (to positive) at the pH of the tumor microenvironment may allow the nanoparticles to be taken up by cancer cells. To prove this concept, charge-invertible nanoparticles modified with novel slightly acidic pH-sensitive peptide (SAPSP-NPs) were developed. The negatively-charged SAPSP-NPs were delivered to tumor tissue, and were successfully taken up by cancer cells upon inversion of the surface charge to positive at intratumoral pH. SAPSP-NPs may serve as an alternative carrier to the PEGylated NP for anti-cancer drug delivery. Copyright © 2015 Elsevier B.V. All rights reserved.
Lin, Ze-Nan; Chen, Jie; Cui, Hong-Ping
Corneal dystrophy is a common type of hereditary corneal diseases. It includes many types, which have varied pathology, histology and clinical manifestations. Recently, the examination techniques of ophthalmology and gene sequencing advance greatly, which do benefit to our understanding of these diseases. However, many aspects remain still unknown. And due to the poor knowledge of these diseases, the results of the treatments are not satisfoctory. The purpose of this review was to summarize the clinical, histological and genetic characteristics of different types of corneal dystrophies. PMID:27366696
Mercieca, Karl; Dharmasena, Aruna; Hopley, Charles
An observational case report of corneal perforation following scleral indentation in a patient with previously undiagnosed pellucid marginal degeneration is presented. Clinical examination, investigations, and subsequent management of this unwarranted and rare complication are described and discussed. The case highlights the need for thorough anterior segment examination before indirect ophthalmoscopy particularly in the presence of ectatic corneal pathology in which case scleral indentation should be avoided. PMID:27146937
Yoon, Jinny J; Ismail, Salim; Sherwin, Trevor
A strong cohort of evidence exists that supports the localisation of corneal stem cells at the limbus. The distinguishing characteristics of limbal cells as stem cells include slow cycling properties, high proliferative potential when required, clonogenicity, absence of differentiation marker expression coupled with positive expression of progenitor markers, multipotency, centripetal migration, requirement for a distinct niche environment and the ability of transplanted limbal cells to regenerate the entire corneal epithelium. The existence of limbal stem cells supports the prevailing theory of corneal homeostasis, known as the XYZ hypothesis where X represents proliferation and stratification of limbal basal cells, Y centripetal migration of basal cells and Z desquamation of superficial cells. To maintain the mass of cornea, the sum of X and Y must equal Z and very elegant cell tracking experiments provide strong evidence in support of this theory. However, several recent studies have suggested the existence of oligopotent stem cells capable of corneal maintenance outside of the limbus. This review presents a summary of data which led to the current concepts of corneal epithelial homeostasis and discusses areas of controversy surrounding the existence of a secondary stem cell reservoir on the corneal surface.
Aicher, Sue A.; Hegarty, Deborah M.; Hermes, Sam M.
Corneal pain is mediated by primary afferent fibers projecting to the dorsal horn of the medulla, specifically the trigeminal nucleus caudalis. In contrast to reflex responses, the conscious perception of pain requires transmission of neural activity to higher brain centers. Ascending pain transmission is mediated primarily by pathways to either the thalamus or parabrachial nuclei. We previously showed that some corneal afferent fibers preferentially contact parabrachial-projecting neurons in the rostral pole of the trigeminal nucleus caudalis, but the role of these projection neurons in transmitting noxious information from the cornea has not been established. In the present study, we show that noxious stimulation of the corneal surface activates neurons in the rostral pole of the nucleus caudalis, including parabrachially projecting neurons that receive direct input from corneal afferent fibers. We used immunocytochemical detection of c-Fos protein as an index of neuronal activation after noxious ocular stimulation. Animals had previously received injections of a retrograde tracer into either thalamic or parabrachial nuclei to identify projection neurons in the trigeminal dorsal horn. Noxious stimulation of the cornea induced c-Fos in neurons sending projections to parabrachial nuclei, but not thalamic nuclei. We also confirmed that corneal afferent fibers identified with cholera toxin B preferentially target trigeminal dorsal horn neurons projecting to the parabrachial nucleus. The parabrachial region sends ascending projections to brain regions involved in emotional and homeostatic responses. Activation of the ascending parabrachial system may explain the extraordinary salience of stimulation of corneal nociceptors. PMID:24418463
Wahl, Christina; Li, Tong; Choden, Tsering; Howland, Howard
In this study we wish to augment our understanding of the effect of environment on corneal growth and morphology. To understand how corneal development of chicks raised in constant light differs from that of 'normal' eyes exposed to cyclic periods of light and dark, white Leghorn chicks were raised under either constant light (approximately 700 lux at cage top) or in 12 h light/12 h dark conditions for up to 12 weeks after hatching. To determine whether corneal expansion is uniform, some birds from each group received corneal tattoos for periodic photographic assessment. By 16 days of age, constant light corneas weighed less than light/dark regimen corneas [7.39 +/- 0.35 mg (SE) vs. 8.47 mg +/- 0.26 mg SE wet weight, P < or = 0.05], and corresponding differences were seen in corneal dry weights. Spatial expansion of the corneal surface was uniform in both groups, but the rate of expansion was slower in constant light chicks [0.0327 +/- 0.009 (SE) vs. 0.144 +/- 0.018 (SE) mm(2) day(-1) for normal chicks, P < or = 0.001]. At 1 day of age, there were 422 +/- 12.5 (SE) stromal cells 0.01 mm(-2) in the central cornea and 393 +/- 21.5 (SE) stromal cells 0.01 mm(-2 )peripherally. Although this difference is not statistically significant, the cell densities in the central cornea were always larger than those of the peripheral cornea in all eight measurements over a 10.5-week period, and this difference is significant (P < or = 0.008, binomial test). Light/dark regimen birds show no such consistent difference in cell densities between central and peripheral corneas. Thus, the density distribution of corneal stromal cells of chicks grown in constant light differs from that of normal chicks. Taken together, all these observations suggest that diurnal cycles of light and darkness are necessary for normal corneal growth.
Thiagarajah, Jay R; Verkman, A S
Two aquaporin (AQP)-type water channels are expressed in mammalian cornea, AQP1 in endothelial cells and AQP5 in epithelial cells. To test whether these aquaporins are involved in corneal fluid transport and transparency, we compared corneal thickness, water permeability, and response to experimental swelling in wild type mice and transgenic null mice lacking AQP1 and AQP5. Corneal thickness in fixed sections was remarkably reduced in AQP1 null mice and increased in AQP5 null mice. By z-scanning confocal microscopy, corneal thickness in vivo was (in microm, mean +/- S.E., n = 5 mice) 123 +/- 1 (wild type), 101 +/- 2 (AQP1 null), and 144 +/- 2 (AQP5 null). After exposure of the external corneal surface to hypotonic saline (100 mosm), the rate of corneal swelling (5.0 +/- 0.3 microm/min, wild type) was reduced by AQP5 deletion (2.7 +/- 0.1 microm/min). After exposure of the endothelial surface to hypotonic saline by anterior chamber perfusion, the rate of corneal swelling (7.1 +/- 1.0 microm/min, wild type) was reduced by AQP1 deletion (1.6 +/- 0.4 microm/min). Base-line corneal transparency was not impaired by AQP1 or AQP5 deletion. However, the recovery of corneal transparency and thickness after hypotonic swelling (10-min exposure of corneal surface to hypotonic saline) was remarkably delayed in AQP1 null mice with approximately 75% recovery at 7 min in wild type mice compared with 5% recovery in AQP1 null mice. Our data indicate that AQP1 and AQP5 provide the principal routes for corneal water transport across the endothelial and epithelial barriers, respectively. The impaired recovery of corneal transparency in AQP1 null mice provides evidence for the involvement of AQP1 in active extrusion of fluid from the corneal stroma across the corneal endothelium. The up-regulation of AQP1 expression and/or function in corneal endothelium may reduce corneal swelling and opacification following injury.
Belin, M W
The PAR Corneal Topography System (CTS) is a computer-driven corneal imaging system that uses close-range raster photogrammetry to measure and produce a topographic map of the corneal surface. The CTS determines distortion in a projected two-dimensional grid. Unlike Placido-disc-based videokeratoscopes, the PAR CTS produces a true topographic map (elevation map) and requires neither a smooth reflective surface nor precise spatial alignment for accurate imaging. Because the system uses two noncoaxial optical paths, it can be integrated into other optical devices. A modified CTS was integrated into an experimental erbium: YAG photoablative laser. The CTS successfully imaged corneas before, after, and during laser photoablation. Its ability to image nonreflective surfaces and to be integrated into other optical systems may make it suitable for intraoperative refractive monitoring.
Shakiba, Yadollah; Mostafaie, Ali
Corneal neovascularization is a significant, sight-threatening complication of many ocular surface disorders. Various growth factors and proteinases are involved in corneal neovascularization. The data supporting a causal role for vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs) are extensive. Inhibition of VEGF and MMPs is a main strategy for treating corneal neovascularization. Several findings have shown that corneal neovascularization can be reduced by using anti-VEGF and anti-MMPs agents. Efficacy of a nutrient mixture (NM) containing lysine, proline, ascorbic acid, and green tea extract has been demonstrated for reducing VEGF and MMPs secretion by various cells. Moreover, NM can inhibit endothelial cell migration and capillary tube formation. We herein note that topical application of NM is potentially useful for inhibiting corneal neovascularization and restoration of corneal clarity. Further investigations in animal models are needed to place NM alongside corneal neovascularization therapeutics.
Fereidouni, Farzad; Datta-Mitra, Ananya; Demos, Stavros; Levenson, Richard
A novel microscopy method that takes advantage of shallow photon penetration using ultraviolet-range excitation and exogenous fluorescent stains is described. This approach exploits the intrinsic optical sectioning function when exciting tissue fluorescence from superficial layers to generate images similar to those obtainable from a physically thinsectioned tissue specimen. UV light in the spectral range from roughly 240-275 nm penetrates only a few microns into the surface of biological specimens, thus eliminating out-of-focus signals that would otherwise arise from deeper tissue layers. Furthermore, UV excitation can be used to simultaneously excite fluorophores emitting across a wide spectral range. The sectioning property of the UV light (as opposed to more conventional illumination in the visible range) removes the need for physical or more elaborate optical sectioning approaches, such as confocal, nonlinear or coherent tomographic methods, to generate acceptable axial resolution. Using a tunable laser, we investigated the effect of excitation wavelength in the 230-350 nm spectral range on excitation depth. The results reveal an optimal wavelength range and suggest that this method can be a fast and reliable approach for rapid imaging of tissue specimens. Some of this range is addressable by currently available and relatively inexpensive LED light sources. MUSE may prove to be a good alternative to conventional, time-consuming, histopathology procedures.
Baehr, E. F. (Inventor)
A corneal seal device is provided which, when placed in an incision in the eye, permits the insertion of a surgical tool or instrument through the device into the eye. The device includes a seal chamber which opens into a tube which is adapted to be sutured to the eye and serves as an entry passage for a tool. A sealable aperture in the chamber permits passage of the tool through the chamber into the tube and hence into the eye. The chamber includes inlet ports adapted to be connected to a regulated source of irrigation fluid which provides a safe intraocular pressure.
Farooq, Asim V; Soin, Ketki; Williamson, Samantha; Joslin, Charlotte E; Cortina, Maria S; Tu, Elmer Y
To report the association of chronic ocular hypotony with the development of progressive corneal ectasia and hydrops. Retrospective case series. Three patients with ocular hypotony were referred for corneal evaluation and found to have ectasia and acute corneal hydrops in their hypotonous eye(s). Clinically, the globes were easily deformable with either external digital palpation and/or simple blinking. All 3 patients had a history of chronic iridocyclitis, including one with juvenile idiopathic arthritis. In each case, the area of thinning was narrow and arcuate in configuration, distinctive from other ectatic disorders. Also uncharacteristically, the acute hydrops resolved rapidly within 2 to 3 weeks without surgical intervention. In 1 case, severe thinning with perforation occurred requiring urgent penetrating keratoplasty. This case series demonstrates a unique clinical entity in which corneal ectasia and hydrops developed in the setting of ocular hypotony and easily deformable corneas, in a pattern unlike previously described forms of ectasia. Acute hydrops, even with associated corneal perforation, demonstrated a short and self-limited course. Corneal ectasia and irregular astigmatism should be suspected as a cause of unexplained visual loss in the ever-increasing number of patients with chronic, stable ocular hypotony. Further study is warranted to determine the pathophysiology of corneal ectasia in this setting, which may include mechanical and inflammatory factors.
Ortiz, Sergio; Siedlecki, Damian; Pérez-Merino, Pablo; Chia, Noelia; de Castro, Alberto; Szkulmowski, Maciej; Wojtkowski, Maciej; Marcos, Susana
We present a method to obtain accurate corneal topography from a spectral optical coherence tomography (sOCT) system. The method includes calibration of the device, compensation of the fan (or field) distortion introduced by the scanning architecture, and image processing analysis for volumetric data extraction, segmentation and fitting. We present examples of three-dimensional (3-D) surface topography measurements on spherical and aspheric lenses, as well as on 10 human corneas in vivo. Results of sOCT surface topography (with and without fan-distortion correction) were compared with non-contact profilometry (taken as reference) on a spherical lens, and with non-contact profilometry and state-of-the art commercial corneal topography instruments on aspheric lenses and on subjects. Corneal elevation maps from all instruments were fitted by quadric surfaces (as well as by tenth-order Zernike polynomials) using custom routines. We found that the discrepancy in the estimated radius of curvature from nominal values in artificial corneas decreased from 4.6% (without fan distortion correction) to 1.6% (after fan distortion correction), and the difference in the asphericity decreased from 130% to 5%. In human corneas, the estimated corneal radius of curvature was not statistically significantly different across instruments. However, a Bland-Altman analysis showed consistent differences in the estimated asphericity and corneal shape between sOCT topographies without fan distortion correction and the rest of the measurements. PMID:22162814
Enders, Philip; Holtick, Udo; Schaub, Friederike; Tuchscherer, Armin; Hermann, Manuel M; Scheid, Christoph; Cursiefen, Claus; Bachmann, Björn O
To assess the capability of Scheimpflug-based densitometry of the cornea to quantify light chain deposits in patients with active monoclonal gammopathies. This is a case-control study in which data from a leading tertiary university center in myeloma care were analyzed. Ten eyes of 5 patients with monoclonal gammopathy and 26 eyes of 13 healthy controls undergoing clinical evaluation and Scheimpflug-based measurements were included in the study. The main outcome measures were densitometry data of the 4 corneal layers-anterior layer (AL), central layer (CL), posterior layer, and total layer (TL)-in 4 different annuli (central annular zone 0-2 mm, intermediate annular zone 2-6 mm, peripheral annular zone 6-10 mm, and total annular zone 0-12 mm). In 8 eyes of 4 patients with IgG-based gammopathy, corneal light backscatter was highest in the AL and decreased with increasing corneal depth. The peripheral annular zone showed a higher densitometry value compared with the corneal center. Compared with healthy controls, the AL (P < 0.001), the CL (P < 0.001), and the TL (P < 0.001) had significantly higher corneal light backscatter in patients with gammopathy in the total and the peripheral annular zones. In one patient with predominantly IgA-based disease, corneal light backscatter was not elevated. Scheimpflug-based densitometry of the cornea is able to quantify opacification by immunoglobulin G light chain deposits in monoclonal gammopathies. This noninvasive technique can complement presently used in vivo confocal microscopy and corneal photography to objectivize corneal changes. Densitometry might allow monitoring of corneal immunoglobulin deposits in follow-up examinations.
Basu, Ishita; Graupe, Daniel; Tuninetti, Daniela; Shukla, Pitamber; Slavin, Konstantin V; Metman, Leo Verhagen; Corcos, Daniel M
We present a proof of concept for a novel method of predicting the onset of pathological tremor using non-invasively measured surface electromyogram (sEMG) and acceleration from tremor-affected extremities of patients with Parkinson's disease (PD) and essential tremor (ET). The tremor prediction algorithm uses a set of spectral (Fourier and wavelet) and nonlinear time series (entropy and recurrence rate) parameters extracted from the non-invasively recorded sEMG and acceleration signals. The resulting algorithm is shown to successfully predict tremor onset for all 91 trials recorded in 4 PD patients and for all 91 trials recorded in 4 ET patients. The predictor achieves a 100% sensitivity for all trials considered, along with an overall accuracy of 85.7% for all ET trials and 80.2% for all PD trials. By using a Pearson's chi-square test, the prediction results are shown to significantly differ from a random prediction outcome. The tremor prediction algorithm can be potentially used for designing the next generation of non-invasive closed-loop predictive ON-OFF controllers for deep brain stimulation (DBS), used for suppressing pathological tremor in such patients. Such a system is based on alternating ON and OFF DBS periods, an incoming tremor being predicted during the time intervals when DBS is OFF, so as to turn DBS back ON. The prediction should be a few seconds before tremor re-appears so that the patient is tremor-free for the entire DBS ON-OFF cycle and the tremor-free DBS OFF interval should be maximized in order to minimize the current injected in the brain and battery usage.
Aicher, S A; Hermes, S M; Hegarty, D M
Dorsal horn neurons send ascending projections to both thalamic nuclei and parabrachial nuclei; these pathways are thought to be critical pathways for central processing of nociceptive information. Afferents from the corneal surface of the eye mediate nociception from this tissue which is susceptible to clinically important pain syndromes. This study examined corneal afferents to the trigeminal dorsal horn and compared inputs to thalamic- and parabrachial-projecting neurons. We used anterograde tracing with cholera toxin B subunit to identify corneal afferent projections to trigeminal dorsal horn, and the retrograde tracer FluoroGold to identify projection neurons. Studies were conducted in adult male Sprague-Dawley rats. Our analysis was conducted at two distinct levels of the trigeminal nucleus caudalis (Vc) which receive corneal afferent projections. We found that corneal afferents project more densely to the rostral pole of Vc than the caudal pole. We also quantified the number of thalamic- and parabrachial-projecting neurons in the regions of Vc that receive corneal afferents. Corneal afferent inputs to both groups of projection neurons were also more abundant in the rostral pole of Vc. Finally, by comparing the frequency of corneal afferent appositions to thalamic- versus parabrachial-projecting neurons, we found that corneal afferents preferentially target parabrachial-projecting neurons in trigeminal dorsal horn. These results suggest that nociceptive pain from the cornea may be primarily mediated by a non-thalamic ascending pathway. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.
Aicher, Sue A.; Hermes, Sam M.; Hegarty, Deborah M.
Dorsal horn neurons send ascending projections to both thalamic nuclei and parabrachial nuclei; these pathways are thought to be critical pathways for central processing of nociceptive information. Afferents from the corneal surface of the eye mediate nociception from this tissue which is susceptible to clinically important pain syndromes. This study examined corneal afferents to the trigeminal dorsal horn and compared inputs to thalamic- and parabrachial-projecting neurons. We used anterograde tracing with cholera toxin B subunit to identify corneal afferent projections to trigeminal dorsal horn, and the retrograde tracer FluoroGold to identify projection neurons. Studies were conducted in adult male Sprague-Dawley rats. Our analysis was conducted at two distinct levels of the trigeminal subnucleus caudalis (Vc) which receive corneal afferent projections. We found that corneal afferents project more densely to the rostral pole of Vc than the caudal pole. We also quantified the number of thalamic- and parabrachial-projecting neurons in the regions of Vc that receive corneal afferents. Corneal afferent inputs to both groups of projection neurons were also more abundant in the rostral pole of Vc. Finally, by comparing the frequency of corneal afferent appositions to thalamic- versus parabrachial-projecting neurons, we found that corneal afferents preferentially target parabrachial-projecting neurons in trigeminal dorsal horn. These results suggest that nociceptive pain from the cornea may be primarily mediated by a non-thalamic ascending pathway. PMID:23201828
Hu, Pei-Hong; Gao, Gui-Ping; Yu, Yao; Pei, Chong-Gang; Zhou, Qiong; Huang, Xin; Zhang, Ying; Shao, Yi
To determine the typical corneal changes in pure microphthalmia using a corneal topography system and identify characteristics that may assist in early diagnosis. Patients with pure microphthalmia and healthy control subjects underwent corneal topography analysis (Orbscan IIZ® Corneal Topography System; Bausch and Lomb, Bridgewater, NJ, USA) to determine degree of corneal astigmatism (mean A), simulation of corneal astigmatism (sim A), mean keratometry (mean K), simulated keratometry (sim K), irregularities in the 3 - and 5-mm zone, and mean thickness of nine distinct corneal regions. Patients with pure microphthalmia (n = 12) had significantly higher mean K, sim K, mean A, sim A, 3.0 mm irregularity and 5.0 mm irregularity, and exhibited significantly more false keratoconus than controls (n = 12). There was a significant between-group difference in the morphology of the anterior corneal surface and the central curvature of the cornea. Changes in corneal morphology observed in this study could be useful in borderline situations to confirm the diagnosis of pure microphthalmia. © The Author(s) 2015.
Khachikian, Stephen S; Belin, Michael W; Ciolino, Joseph B
To establish the normal distribution for intrasubject (right eye/left eye) central corneal pachymetry in a refractive surgery population. A retrospective analysis was performed on 1448 eyes of 724 consecutive patients evaluated for refractive surgery. Pachymetric data were obtained from the Pentacam Eye Scanner. Right and left eye pachymetry values were compared for the corneal apex, pupil center, and thinnest point. Statistical analysis was performed to determine normal levels of variance. The average apex reading was 539.3+/-36.8 microm, median 542 microm, and mode 539 microm (range: 411 to 664 microm). Values for the pupil center (average 538.7 microm) and thinnest point (average 536.1 microm) followed a similar distribution. The average pachymetry difference between fellow eyes was 8.8+/-7.2 microm at the apex, 8.9+/-8.3 microm at the pupil center, and 9.0+/-8.3 microm at the thinnest region. Individuals with a greater than 23.2 microm apical pachymetry difference represent less than 5% of the population. Individuals with an apical difference greater than 30.4 microm represent less than 0.5%. Pachymetric asymmetry outside the normal range should alert the clinician to examine for other parameters that are more established refractive surgery risk factors.
Meek, Keith M.; Knupp, Carlo
The corneal stroma plays several pivotal roles within the eye. Optically, it is the main refracting lens and thus has to combine almost perfect transmission of visible light with precise shape, in order to focus incoming light. Furthermore, mechanically it has to be extremely tough to protect the inner contents of the eye. These functions are governed by its structure at all hierarchical levels. The basic principles of corneal structure and transparency have been known for some time, but in recent years X-ray scattering and other methods have revealed that the details of this structure are far more complex than previously thought and that the intricacy of the arrangement of the collagenous lamellae provides the shape and the mechanical properties of the tissue. At the molecular level, modern technologies and theoretical modelling have started to explain exactly how the collagen fibrils are arranged within the stromal lamellae and how proteoglycans maintain this ultrastructure. In this review we describe the current state of knowledge about the three-dimensional stromal architecture at the microscopic level, and about the control mechanisms at the nanoscopic level that lead to optical transparency. PMID:26145225
Meek, Keith M; Knupp, Carlo
The corneal stroma plays several pivotal roles within the eye. Optically, it is the main refracting lens and thus has to combine almost perfect transmission of visible light with precise shape, in order to focus incoming light. Furthermore, mechanically it has to be extremely tough to protect the inner contents of the eye. These functions are governed by its structure at all hierarchical levels. The basic principles of corneal structure and transparency have been known for some time, but in recent years X-ray scattering and other methods have revealed that the details of this structure are far more complex than previously thought and that the intricacy of the arrangement of the collagenous lamellae provides the shape and the mechanical properties of the tissue. At the molecular level, modern technologies and theoretical modelling have started to explain exactly how the collagen fibrils are arranged within the stromal lamellae and how proteoglycans maintain this ultrastructure. In this review we describe the current state of knowledge about the three-dimensional stromal architecture at the microscopic level, and about the control mechanisms at the nanoscopic level that lead to optical transparency. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.
Luz, Allan; Lopes, Bernardo; Salomão, Marcela; Ambrósio, Renato
Ectasia after refractive surgery represents a major concern among refractive surgeons. Corneal abnormalities and preexisting corneal ectasia are the most important risk factors. Corneal topography and central corneal thickness are the factors traditionally screening for in refractive surgery candidates. Study of the anterior surface by Placido topography allows for identification of keratoconus before biomicroscopy. However, this is insufficient for the evaluation of pre-operative refractive surgery. There are cases of ectasia after laser in situ keratomilusis (LASIK) without identifiable risk factors such that there is a need to go beyond the corneal surface. A key requirement is quantifying susceptibility to corneal biomechanical instability and progression to ectasia. Tomographic indices derived from elevation maps and pachymetry spatial variation produce a Belin Ambrosio display final D index (BAD-D index), which has shown better results compared to surface curvature indices for detecting very mild forms of ectasia. A logistic regression formula, integrating age, residual stromal bed, and BAD-D (Ectasia Susceptibility Score, ESS) resulted in a significant improvement in accuracy, leading to 100% sensitivity and 94% specificity for detecting susceptible cases. A comprehensive corneal structural analysis based on corneal segmental tomography can detect susceptible corneas, which increases safety for refractive surgery patients. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Suryawanshi, Amol; Cao, Zhiyi; Thitiprasert, Thananya; Zaidi, Tanveer S; Panjwani, Noorjahan
Corneal infection with Pseudomonas aeruginosa leads to a severe immunoinflammatory lesion, often causing vision impairment and blindness. Although past studies have indicated a critical role for CD4(+) T cells, particularly Th1 cells, in corneal immunopathology, the relative contribution of recently discovered Th17 and regulatory T cells is undefined. In this study, we demonstrate that after corneal P. aeruginosa infection, both Th1 and Th17 cells infiltrate the cornea with increased representation of Th17 cells. In addition to Th1 and Th17 cells, regulatory T cells also migrate into the cornea during early as well as late stages of corneal pathology. Moreover, using galectin-1 (Gal-1), an immunomodulatory carbohydrate-binding molecule, we investigated whether shifting the balance among various CD4(+) T cell subsets can modulate P. aeruginosa-induced corneal immunopathology. We demonstrate in this study that local recombinant Gal-1 (rGal-1) treatment by subconjunctival injections significantly diminishes P. aeruginosa-mediated corneal inflammation through multiple mechanisms. Specifically, in our study, rGal-1 treatment significantly diminished corneal infiltration of total CD45(+) T cells, neutrophils, and CD4(+) T cells. Furthermore, rGal-1 treatment significantly reduced proinflammatory Th17 cell response in the cornea as well as local draining lymph nodes. Also, rGal-1 therapy promoted anti-inflammatory Th2 and IL-10 response in secondary lymphoid organs. Collectively, our results indicate that corneal P. aeruginosa infection induces a strong Th17-mediated corneal pathology, and treatment with endogenously derived protein such as Gal-1 may be of therapeutic value for the management of bacterial keratitis, a prevalent cause of vision loss and blindness in humans worldwide.
Whitcher, J. P.; Srinivasan, M.; Upadhyay, M. P.
Diseases affecting the cornea are a major cause of blindness worldwide, second only to cataract in overall importance. The epidemiology of corneal blindness is complicated and encompasses a wide variety of infectious and inflammatory eye diseses that cause corneal scarring, which ultimately leads to functional blindness. In addition, the prevalence of corneal disease varies from country to country and even from one population to another. While cataract is responsible for nearly 20 million of the 45 million blind people in the world, the next major cause is trachoma which blinds 4.9 million individuals, mainly as a result of corneal scarring and vascularization. Ocular trauma and corneal ulceration are significant causes of corneal blindness that are often underreported but may be responsible for 1.5-2.0 million new cases of monocular blindness every year. Causes of childhood blindness (about 1.5 million worldwide with 5 million visually disabled) include xerophthalmia (350,000 cases annually), ophthalmia neonatorum, and less frequently seen ocular diseases such as herpes simplex virus infections and vernal keratoconjunctivitis. Even though the control of onchocerciasis and leprosy are public health success stories, these diseases are still significant causes of blindness--affecting a quarter of a million individuals each. Traditional eye medicines have also been implicated as a major risk factor in the current epidemic of corneal ulceration in developing countries. Because of the difficulty of treating corneal blindness once it has occurred, public health prevention programmes are the most cost-effective means of decreasing the global burden of corneal blindness. PMID:11285665
Damian, Angela; Seitz, Berthold; Langenbucher, Achim; Eppig, Timo
Vision loss due to corneal injuries or diseases can be treated by transplantation of human corneal grafts (keratoplasty). However, quality assurance in retrieving and cultivating the tissue transplants is confined to visual and microbiological testing. To identify previous refractive surgery or morphological alterations, an automatic, noncontact, sterile screening procedure is required. Twenty-three corneal grafts have been measured in organ culture with a clinical spectral-domain optical coherence tomographer. Employing a biconic surface fit with 10 degrees of freedom, the radii of curvature and conic constants could be estimated for the anterior and posterior corneal surfaces. Thereupon, central corneal thickness, refractive values, and astigmatism have been calculated. Clinical investigations are required to elaborate specific donor-host matching in the future.
Steven, Philipp; Bock, Felix; Hüttmann, Gereon; Cursiefen, Claus
The role of lymphatic vessels in tissue and organ transplantation as well as in tumor growth and metastasis has drawn great attention in recent years. We now developed a novel method using non-invasive two-photon microscopy to simultaneously visualize and track specifically stained lymphatic vessels and autofluorescent adjacent tissues such as collagen fibrils, blood vessels and immune cells in the mouse model of corneal neovascularization in vivo. The mouse cornea serves as an ideal tissue for this technique due to its easy accessibility and its inducible and modifiable state of pathological hem- and lymphvascularization. Neovascularization was induced by suture placement in corneas of Balb/C mice. Two weeks after treatment, lymphatic vessels were stained intravital by intrastromal injection of a fluorescently labeled LYVE-1 antibody and the corneas were evaluated in vivo by two-photon microscopy (TPM). Intravital TPM was performed at 710 nm and 826 nm excitation wavelengths to detect immunofluorescence and tissue autofluorescence using a custom made animal holder. Corneas were then harvested, fixed and analyzed by histology. Time lapse imaging demonstrated the first in vivo evidence of immune cell migration into lymphatic vessels and luminal transport of individual cells. Cells immigrated within 1-5.5 min into the vessel lumen. Mean velocities of intrastromal corneal immune cells were around 9 µm/min and therefore comparable to those of T-cells and macrophages in other mucosal surfaces. To our knowledge we here demonstrate for the first time the intravital real-time transmigration of immune cells into lymphatic vessels. Overall this study demonstrates the valuable use of intravital autofluorescence two-photon microscopy in the model of suture-induced corneal vascularizations to study interactions of immune and subsequently tumor cells with lymphatic vessels under close as possible physiological conditions.
Ondas, Osman; Keles, Sadullah
Background The aim of this study was to evaluate central corneal thickness in patients with atopic keratoconjunctivitis. Material/Methods The study was conducted in the Atatürk University School of Medicine between April 2011 and June 2013. The study group included 60 eyes of 30 patients with atopic keratoconjunctivitis. Sixty eyes of 30 healthy individuals without any ophthalmic or systemic pathology were used as a control group. The central corneal thickness was measured with ultrasonic pachymetry. Results In each group, all subjects included in the study had a best corrected visual acuity (BCVA) of 20/25 or better. In the study group past medical histories revealed eczema in 19 patients, asthma in 16, and atopic dermatitis in 15. During clinical examination cicatricial conjunctivitis was noted in 5 patients, giant papillae in 4, symblepharon in 2, and entropion in 2. The mean central corneal thickness was 523.45±18.03 μm in the study group (mean age: 37.05±5.7 years) and 540.30±38.91 μm in the control group (mean age: 36.55±7.1 years), and the difference was statistically significant (p<0.001). Conclusions Evaluation of corneal thickness is important in situations such as corneal refractive surgery and contact lens use, and is an essential parameter in a wide range of ocular disorders, including glaucoma and keratoconus. Therefore, ophthalmologists should be aware of the low central corneal thickness in patients with atopic keratoconjunctivitis. PMID:25240805
Maharana, Prafulla K; Dubey, Aditi; Jhanji, Vishal; Sharma, Namrata; Das, Sujata; Vajpayee, Rasik B
Corneal ectasias include a group of disorders characterised by progressive thinning, bulging and distortion of the cornea. Keratoconus is the most common disease in this group. Other manifestations include pellucid marginal degeneration, Terrien's marginal degeneration, keratoglobus and ectasias following surgery. Advanced ectasias usually present with loss of vision due to high irregular astigmatism. Management of these disorders is difficult due to the peripheral location of ectasia and associated severe corneal thinning. Newer contact lenses such as scleral lenses are helpful in a selected group of patients. A majority of these cases requires surgical intervention. This review provides an update on the current treatment modalities available for management of advanced corneal ectasias.
Schmitz, K; Lang, G K; Behrens-Baumann, W
for trephination with individualised transplant geometries appears to be a valuable addition to the surgical repertoire in the presence of selected corneal pathologies.
Figueroa-Ortiz, L C; Martín Rodríguez, O; García-Ben, A; García-Campos, J
To analyse the length and area of corneal surface occupied by vessels, and their location in an experimental model of alkali burn-induced corneal neovascularization. An injury to the central cornea of the right eye in 91 Sprague-Dawley rats was induced using a silver nitrate pencil. The rats were divided in 7 groups that were sacrificed 2, 4, 6, 8, 10, 12 and 14 days post-injury, and then perfused with a mixture of Chinese ink in PBS -phosphate buffer saline-. Corneas were flat-mounted processed and divided in 4 quadrants. Corneal neovascular growth parameters (length and area) and the location of these vessels were performed blind. The results were statistically analysed. Neovascular growth was observed from day 2, reaching its maximum peak in length and area on the 12th day post-injury. A slight reduction in corneal neovascularization was observed after this day. The vessels were initially located in the middle third of the stroma and tended to be observed in the anterior third during the course of the experiment. Neovascularisation was observed on day 2 post-injury in all sectors of corneal surface. Neovascular growth was uniform during the experiment. Neovessels were located in the middle and anterior third of the cornea. Copyright © 2012 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.
Hodson, S; O'Leary, D; Watkins, S
1. Ox corneal stromal swelling pressure (gel pressure) may be measured by osmometry: polyethylene glycol of nominal molecular mass 10,000 Da (PEG 10K) is a suitable non-penetrating solute. 2. Corneal hydrations equilibrate within 4 h of exposure to 154 mM-NaCl including various concentrations (2-8%) of PEG 10K, providing that the epithelium covers the anterior surface and Descemet's membrane covers the posterior surface. At equilibrium hydration, corneal gel pressure equals the external osmotic pressure contributed by PEG 10K. 3. The osmotic pressure of PEG 10K may be calibrated using Descemet's membrane as the semi-permeable membrane. 4. Corneal gel pressure decreases with increasing hydration. 5. The relationship may be adequately explained by the Donnan theory of corneal swelling with a fixed negative matrix charge of 39.5 +/- 0.8 mequiv l-1 at physiological hydration of 3.2 at this salt concentration (154 mM-NaCl). PMID:2023123
Lim, Chris H L; Turner, Angus; Lim, Blanche X
Published audits have demonstrated that corneal abrasions are a common presenting eye complaint. Eye patches are often recommended for treating corneal abrasions despite the lack of evidence for their use. This systematic review was conducted to determine the effects of the eye patch when used to treat corneal abrasions. The objective of this review was to assess the effects of patching for corneal abrasion on healing and pain relief. We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2016, Issue 4), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to May 2016), EMBASE (January 1980 to May 2016), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to May 2016), System for Information on Grey Literature in Europe (OpenGrey) (January 1995 to May 2016), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 9 May 2016. We also searched the reference lists of included studies, unpublished 'grey' literature and conference proceedings and contacted pharmaceutical companies for details of unpublished trials. We included randomised and quasi-randomised controlled trials that compared patching the eye with no patching to treat simple corneal abrasions. Two authors independently assessed the risk of bias and extracted data. Investigators were contacted for further information regarding the quality of trials. The primary outcome was healing at 24, 48 and 72 hours while secondary outcomes included measures of pain, quality of life and adverse effects. We graded the certainty of the evidence using GRADE. We included 12 trials which
Zhou, Wen; Stojanovic, Aleksandar; Utheim, Tor Paaske
The aim of the study is to raise the awareness of the influence of coma-like higher-order aberrations (HOAs) on power and orientation of refractive astigmatism (RA) and to explore how to account for that influence in the planning of topography-guided refractive surgery in eyes with coma-like-aberrations-dominant corneal optics. Eleven eyes with coma-like-aberrations-dominant corneal optics and with low lenticular astigmatism (LA) were selected for astigmatism analysis and for treatment simulations with topography-guided custom ablation. Vector analysis was used to evaluate the contribution of coma-like corneal HOAs to RA. Two different strategies were used for simulated treatments aiming to regularize irregular corneal optics: With both strategies correction of anterior corneal surface irregularities (corneal HOAs) were intended. Correction of total corneal astigmatism (TCA) and RA was intended as well with strategies 1 and 2, respectively. Axis of discrepant astigmatism (RA minus TCA minus LA) correlated strongly with axis of coma. Vertical coma influenced RA by canceling the effect of the with-the-rule astigmatism and increasing the effect of the against-the-rule astigmatism. After simulated correction of anterior corneal HOAs along with TCA and RA (strategies 1 and 2), only a small amount of anterior corneal astigmatism (ACA) and no TCA remained after strategy 1, while considerable amount of ACA and TCA remained after strategy 2. Coma-like corneal aberrations seem to contribute a considerable astigmatic component to RA in eyes with coma-like-aberrations dominant corneal optics. If topography-guided ablation is programmed to correct the corneal HOAs and RA, the astigmatic component caused by the coma-like corneal HOAs will be treated twice and will result in induced astigmatism. Disregarding RA and treating TCA along with the corneal HOAs is recommended instead.
Findlay, Amy S; Panzica, D Alessio; Walczysko, Petr; Holt, Amy B; Henderson, Deborah J; West, John D; Rajnicek, Ann M; Collinson, J Martin
This study shows that the core planar cell polarity (PCP) genes direct the aligned cell migration in the adult corneal epithelium, a stratified squamous epithelium on the outer surface of the vertebrate eye. Expression of multiple core PCP genes was demonstrated in the adult corneal epithelium. PCP components were manipulated genetically and pharmacologically in human and mouse corneal epithelial cells in vivo and in vitro. Knockdown of VANGL2 reduced the directional component of migration of human corneal epithelial (HCE) cells without affecting speed. It was shown that signalling through PCP mediators, dishevelled, dishevelled-associated activator of morphogenesis and Rho-associated protein kinase directs the alignment of HCE cells by affecting cytoskeletal reorganization. Cells in which VANGL2 was disrupted tended to misalign on grooved surfaces and migrate across, rather than parallel to the grooves. Adult corneal epithelial cells in which Vangl2 had been conditionally deleted showed a reduced rate of wound-healing migration. Conditional deletion of Vangl2 in the mouse corneal epithelium ablated the normal highly stereotyped patterns of centripetal cell migration in vivo from the periphery (limbus) to the centre of the cornea. Corneal opacity owing to chronic wounding is a major cause of degenerative blindness across the world, and this study shows that Vangl2 activity is required for directional corneal epithelial migration.
Findlay, Amy S.; Panzica, D. Alessio; Walczysko, Petr; Holt, Amy B.; Henderson, Deborah J.; West, John D.; Rajnicek, Ann M.
This study shows that the core planar cell polarity (PCP) genes direct the aligned cell migration in the adult corneal epithelium, a stratified squamous epithelium on the outer surface of the vertebrate eye. Expression of multiple core PCP genes was demonstrated in the adult corneal epithelium. PCP components were manipulated genetically and pharmacologically in human and mouse corneal epithelial cells in vivo and in vitro. Knockdown of VANGL2 reduced the directional component of migration of human corneal epithelial (HCE) cells without affecting speed. It was shown that signalling through PCP mediators, dishevelled, dishevelled-associated activator of morphogenesis and Rho-associated protein kinase directs the alignment of HCE cells by affecting cytoskeletal reorganization. Cells in which VANGL2 was disrupted tended to misalign on grooved surfaces and migrate across, rather than parallel to the grooves. Adult corneal epithelial cells in which Vangl2 had been conditionally deleted showed a reduced rate of wound-healing migration. Conditional deletion of Vangl2 in the mouse corneal epithelium ablated the normal highly stereotyped patterns of centripetal cell migration in vivo from the periphery (limbus) to the centre of the cornea. Corneal opacity owing to chronic wounding is a major cause of degenerative blindness across the world, and this study shows that Vangl2 activity is required for directional corneal epithelial migration. PMID:27853583
Dean, B S; Krenzelok, E P
Cyanoacrylate-containing adhesives such as Super Glue, Krazy Glue, and a vast array of artificial nail adhesives are monomers which rapidly polymerize and bond in the presence of water or weak bases. Inadvertent contact with skin or tissue can also cause rapid bonding with resultant irritation. To assess the magnitude of problems associated with ocular contamination involving cyanoacrylates, a 12-month prospective study was conducted. 34 cases (21 adult and 13 pediatric) were collected. In all cases, contaminated eyes were thoroughly irrigated with tepid water for 15 minutes. 15 patients (44%) suffered a corneal abrasion, as determined by ophthalmic exam, necessitating treatment with antibiotics, cycloplegics, and patching. Individuals reporting complete resolution were irrigated with 20 minutes of exposure, while patients suffering mechanical injury delayed decontamination for a minimum of 15 minutes. In addition to immediate irrigation of eyes exposed to cyanoacrylates, we recommend an ophthalmologic evaluation to rule out the possibility of mechanical injury.
Alnawaiseh, Maged; Zumhagen, Lars; Zumhagen, Sven; Schulte, Lea; Rosentreter, André; Schubert, Friederike; Eter, Nicole; Mönnig, Gerold
The clinical efficacy and toxicity of amiodarone may be determined more effectively by tissue deposition than by levels of the agent in serum. Therefore, corneal densitometry might be useful for therapeutic monitoring. The aim of the study is to evaluate Scheimpflug corneal densitometry in patients with amiodarone keratopathy (AK). Comparative case series. Sixty-six patients receiving amiodarone therapy and 66 healthy controls were consecutively enrolled in this study. Patients were examined using the Oculus Pentacam (Wetzlar, Germany). Densitometry data from different corneal layers and different annuli were extracted, analyzed, and compared with densitometry values of healthy controls. Duration of treatment, cumulative dose, Orlando stage (slit-lamp biomicroscopy), and serum concentrations of amiodarone and N-desethylamiodarone also were determined, and the correlation to different densitometry data was evaluated. The total corneal light backscatter at total corneal thickness and at total diameter was significantly higher in the amiodarone group compared with the control group (AK group: 28.3±5.2; control group: 24.4±4.2; P < 0.001). Upon dividing the corneal surface into different layers at total thickness, the differences were significant in all layers (P < 0.001). The serum concentrations of the metabolite N-desethylamiodarone correlate with densitometry values, especially in the 0- to 2-mm annulus in the anterior layer (r = 0.419; P = 0.001), whereas the cumulative dose and duration of treatment correlate significantly with the densitometry values in the 0- to 2-mm annulus at total thickness (P = 0.014 and P = 0.022, respectively). Corneal densitometry is a useful, objective method for quantifying AK and can help in monitoring amiodarone therapy. The serum concentration of the active metabolite N-desethylamiodarone correlates with the extent of keratopathy in the anterior layer, whereas chronic changes in the stroma correlate with the cumulative dose
Niederkorn, Jerry Y.
Corneal transplants have been successfully performed in human subjects for over 100 years and enjoy an immune privilege that is unrivaled in the field of transplantation. Immune privilege is defined as the reduced incidence and tempo in the immune rejection of corneal allografts compared to other categories of organ allografts performed under the same conditions. Skin allografts transplanted across various MHC or minor histocompatibility barriers undergo rejection in approximately 100% of the hosts. By contrast, orthotopic corneal allografts experience long-term survival in 50% to >90% of the hosts, depending on the histocompatibility barriers that confront the host. The capacity of corneal allografts to evade immune rejection is attributable to multiple anatomical, physiological, and immunoregulatory conditions that conspire to prevent the induction and expression of alloimmunity. PMID:23360158
Okumura, Naoki; Kakutani, Kazuya; Inoue, Ryota; Matsumoto, Daiki; Shimada, Tomoki; Nakahara, Makiko; Kiyanagi, Yumiko; Itoh, Takehiro; Koizumi, Noriko
The corneal endothelium maintains corneal transparency by its pump and barrier functions; consequently, its decompensation due to any pathological reason causes severe vision loss due to corneal haziness. Corneal transplantation is the only therapeutic choice for treating corneal endothelial dysfunction, but associated problems, such as a shortages of donor corneas, the difficulty of the surgical procedure, and graft failure, still need to be resolved. Regenerative medicine is attractive to researchers as a means of providing innovative therapies for corneal endothelial dysfunction, as it now does for other diseases. We previously demonstrated the successful regeneration of corneal endothelium in animal models by injecting cultured corneal endothelial cells (CECs) in combination with a Rho kinase (ROCK) inhibitor. The purpose of the present study was to optimize the vehicle for clinical use in cell-based therapy. Our screening of cell culture media revealed that RELAR medium promoted CEC adhesion. We then modified RELAR medium by removing hormones, growth factors, and potentially toxic materials to generate a cell therapy vehicle (CTV) composed of amino acid, salts, glucose, and vitamins. Injection of CECs in CTV enabled efficient engraftment and regeneration of the corneal endothelium in the rabbit corneal endothelial dysfunction model, with restoration of a transparent cornea. The CECs retained >85% viability after a 24 hour preservation as a cell suspension in CTV at 4°C and maintained their potency to regenerate the corneal endothelium in vivo. The vehicle developed here is clinically applicable for cell-based therapy aimed at treating the corneal endothelium. Our strategy involves the generation of vehicle from a culture medium appropriate for a given cell type by removing materials that are not favorable for clinical use. PMID:27355373
Okumura, Naoki; Koizumi, Noriko; Ueno, Morio; Sakamoto, Yuji; Takahashi, Hiroaki; Tsuchiya, Hideaki; Hamuro, Junji; Kinoshita, Shigeru
Corneal endothelial dysfunction accompanied by visual disturbance is a primary indication for corneal transplantation. We previously reported that the adhesion of corneal endothelial cells (CECs) to a substrate was enhanced by the selective ROCK inhibitor Y-27632. It is hypothesized that the inhibition of ROCK signaling may manipulate cell adhesion properties, thus enabling the transplantation of cultivated CECs as a form of regenerative medicine. In the present study, using a rabbit corneal endothelial dysfunction model, the transplantation of CECs in combination with Y-27632 successfully achieved the recovery of corneal transparency. Complications related to cell injection therapy, such as the abnormal deposition of the injected cells as well as the elevation of intraocular pressure, were not observed. Reconstructed corneal endothelium with Y-27632 exhibited a monolayer hexagonal cell shape with a normal expression of function-related markers, such as ZO-1, and Na(+)/K(+)-ATPase, whereas reconstruction without Y-27632 exhibited a stratified fibroblastic phenotype without the expression of markers. Moreover, transplantation of CECs in primates in the presence of the ROCK inhibitor also achieved the recovery of long-term corneal transparency with a monolayer hexagonal cell phenotype at a high cell density. Taken together, these results suggest that the selective ROCK inhibitor Y-27632 enables cultivated CEC-based therapy and that the modulation of Rho-ROCK signaling activity serves to enhance cell engraftment for cell-based regenerative medicine. Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
Jankov II, Mirko R.; Jovanovic, Vesna; Nikolic, Ljubisa; Lake, Jonathan C.; Kymionis, Georgos; Coskunseven, Efekan
Corneal collagen cross-linking (CXL) with riboflavin and ultraviolet-A (UVA) is a new technique of corneal tissue strengthening by using riboflavin as a photosensitizer and UVA to increase the formation of intra and interfibrillar covalent bonds by photosensitized oxidation. Keratocyte apoptosis in the anterior segment of the corneal stroma all the way down to a depth of about 300 microns has been described and a demarcation line between the treated and untreated cornea has been clearly shown. It is important to ensure that the cytotoxic threshold for the endothelium has not been exceeded by strictly respecting the minimal corneal thickness. Confocal microscopy studies show that repopulation of keratocytes is already visible 1 month after the treatment, reaching its pre-operative quantity and quality in terms of functional morphology within 6 months after the treatment. The major indication for the use of CXL is to inhibit the progression of corneal ectasias, such as keratoconus and pellucid marginal degeneration. CXL may also be effective in the treatment and prophylaxis of iatrogenic keratectasia, resulting from excessively aggressive photoablation. This treatment has also been used to treat infectious corneal ulcers with apparent favorable results. Combination with other treatments, such as intracorneal ring segment implantation, limited topography-guided photoablation and conductive keratoplasty have been used with different levels of success. PMID:20543933
Williams, Keryn A; Irani, Yazad D
Despite ever-increasing understanding of the genetic underpinnings of many corneal dystrophies, gene therapy designed to ameliorate disease has not yet been reported in any human patient. In this review, we explore the likely reasons for this apparent failure of translation. We identify the requirements for success: the genetic defect involved must have been identified and mapped, vision in the affected patient must be significantly impaired or likely to be impaired, no better or equivalently effective treatment must be available, the treatment must be capable of modulating corneal pathology, and delivery of the construct to the appropriate cell must be practicable. We consider which of the corneal dystrophies might be amenable to treatment by genetic manipulations, summarize existing therapeutic options for treatment, and explore gene editing using clustered regularly interspaced short palindromic repeat/Cas and other similar transformative technologies as the way of the future. We then summarize recent laboratory-based advances in gene delivery and the development of in vitro and in vivo models of the corneal dystrophies. Finally, we review recent experimental work that has increased our knowledge of the pathobiology of these conditions.
Xuan, Meng; Wang, Shurong; Liu, Xin; He, Yuxi; Li, Ying; Zhang, Yan
The human cornea, consisting of five layers, is the transparent tissue that refracts and transmits light to the lens and retina, providing about two thirds of the refractive power of the eye. The stroma layer comprises nearly 90 % of the thickness of the cornea and thus plays a pivotal role in normal visual function. The bulk of this layer is constituted by proteins in the extracellular martrix secreted by the corneal epithelial, stroma, and endothelial cells. Clinical research has shown that corneal stroma diseases are common and involve conditions such as infections, injuries, and genetic defects, which cause severe visual disturbances or even blindness. To improve our understanding of the basic molecular mechanisms involved in the physiological and pathological activities of the corneal stroma, its proteins have been brought into the limelight to determine their crucial and irreplaceable roles. The data presented in a previous study have demonstrated the presence of 1679 proteins in the stroma, and this data set has subsequently been perfected by utilizing a highly sensitive isobaric peptide-labeling approach. According to their manifestations, these proteins can be classified as a gel-like organic material composed of proteoglycans, enzymes, and hemocyanin-binding proteins and a network of filaments composed of collagen, elastin, keratin, vimentin, and interconnected filaments comprising fibronectin and laminin. The aim of this review is to describe some corneal stroma proteins by highlighting their major functions and valuable applications in ophthalmologic research toward the better characterization and treatment of eye diseases.
Donate, D; Albert, O; Colliac, J-P; Tubelis, P; Sabatier, P; Mourou, G; Burillon, C; Pouliquen, Y; Legeais, J-M
The authors present the diode-pumped, all-solid state, neodymium:glass femtosecond laser from the Laboratory of Ocular Biotechnology, Hotel-Dieu Hospital. We worked with a 1,065-nm wavelength infrared laser. This laser is composed of an oscillator and amplification glass matrix mixed with neodymium. Its stretching and compression system is capable of producing pulses lasting a few hundred femtoseconds. The repetition rate is adjustable, ranging from 1 to 10 kHz, and can reach energies up to 60 microJ. The delivery system was set up on an optical table, with human corneal samples fixed to an anterior chamber system, which can be moved over the X-Y-Z axis by a computer-guided translation motor with micrometric precision. We analyzed the biological effects of laser impacts in human corneal tissue, obtained from the French Eye Bank. The femtosecond laser provides automated corneal cutting with a high level of precision, which can be verified on the corneal surface regularity by scanning electron microscopy analysis. Silicon samples can also be cut and can be used for calibration testing of the laser. The set-up composed of the femtosecond laser and the described delivery system enable precise corneal cutting and offer the opportunity to study its characteristics.
Ishioka, Misaki; Kato, Naoko; Kobayashi, Akira; Dogru, Murat; Tsubota, Kazuo
To study the effect of rinsing with tap and pool water on the ocular surface epithelium. Twenty eyes of 10 volunteers were irrigated in the following order with 250 mL (50 seconds) of physiological salt solution (PSS), distilled water (DW), tap water, or PSS with chlorine (0.5 mg/L). The pH of each fluid was 6.4, 6.8, 6.8, and 6.4, respectively. Vital staining, fluorophotometric assessment, and confocal microscopy were performed before and after irrigation with each fluid. Eyes irrigated with PSS with chlorine showed an increase in fluorescein scores, and eyes washed with both tap water and PSS with chlorine showed an increase in Rose Bengal scores. Corneal fluorescein uptake measured by anterior fluorometer was not altered by eye irrigation with PSS, DW, or tap water. However, PSS with chlorine resulted in a significant increase in corneal fluorescein uptake. Confocal microscopy showed corneal epithelial cell damage in eyes rinsed with PSS with chlorine. Chlorine was determined to be potentially harmful to the corneal epithelial barrier. This study indicated the possibility that swimming without goggles might become a risk factor for corneal epithelial integrity, suggesting encouragement of goggle wear while swimming.
Mourant, J.R.; Bigio, I.J.; Johnson, T.; Shimada, T.; Gritz, D.C.; Storey-Held, K.
The potential of a rapid noninvasive diagnostic system to detect tissue abnormalities on the surface of the eye has been investigated. The optical scatter signal from lesions and normal areas on the conjunctival sclera of the human eye were measured in vivo. It is possible to distinguish nonpigmented pingueculas from other lesions. The ability of the system to detect malignancies could not be tested because none of the measured and biopsied lesions were malignant. Optical scatter and fluorescence spectra of bacterial and fungal suspensions, and corneal irritations were also collected. Both scattering and fluorescence show potential for diagnosing corneal infections.
Alzubaidi, Rania; Sharif, Mhd Saeed; Qahwaji, Rami; Ipson, Stanley; Brahma, Arun
There is an evolution in the demands of modern ophthalmology from descriptive findings to assessment of cellular-level changes by using in vivo confocal microscopy. Confocal microscopy, by producing greyscale images, enables a microstructural insight into the in vivo cornea in both health and disease, including epithelial changes, stromal degenerative or dystrophic diseases, endothelial pathologies and corneal deposits and infections. Ophthalmologists use acquired confocal corneal images to identify health and disease states and then to diagnose which type of disease is affecting the cornea. This paper presents the main features of the healthy confocal corneal layers and reviews the most common corneal diseases. It identifies the visual signatures of each disease in the affected layer and extracts the main features of this disease in terms of intensity, certain regular shapes with both their size and diffusion, and some specific region of interest. These features will lead towards the development of a complete automatic corneal diagnostic system that predicts abnormalities in the confocal corneal data sets. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
Erdey, R A; Lindahl, K J; Temnycky, G O; Aquavella, J V
We describe a modified technique of using cyanoacrylate adhesive to seal corneal perforations. Easily performed at the slit lamp, its advantages over previously described methods include a smooth, contoured collagen surface overlying the adhesive, which is easily wet by the tear film. Even greater comfort and protection are provided by the addition of a hydrophilic bandage lens or collagen shield.
Corneal Scheimpflug tomography is a commonly used non-invasive imaging technique. This review article summarizes the principles of the technique and recent results from the literature with a focus on keratoconus diagnostics. Review of the literature, own data and expert opinions. Corneal Scheimpflug tomography allows topography of the anterior and posterior surfaces as well as spatially resolved pachymetry and densitometry. Measurements obtained with currently available systems are highly reproducible but not interchangeable. Combining topographic and pachymetric data allows a highly sensitive and specific diagnostic modality for the early diagnosis of keratoconus. Due to the versatility, precision and easy handling, corneal Scheimpflug tomography is the most important imaging technique for the anterior segment of the eye.
Walczysko, Petr; Rajnicek, Ann M.
Purpose Patients with a heterozygous mutation in the gene encoding the transcription factor, PAX6, have a degenerative corneal opacity associated with failure of normal radial epithelial cell migration across the corneal surface and a reported wound healing defect. This study investigated the guidance mechanisms that drive the directed migration of corneal epithelial cells. Methods In vivo corneal epithelial wounding was performed in adult wild-type and Pax6+/− mice, and the healing migration rates were compared. To investigate the control of the cell migration direction, primary corneal epithelial cells from wild-type and Pax6+/− mice were plated on grooved quartz substrates, and alignment relative to the grooves was assayed. A reconstructed corneal culture system was developed in which dissociated wild-type and genetically mutant corneal epithelial cells could be cultured on a de-epithelialized corneal stroma or basement membrane and their migration assayed with time-lapse microscopy. Results The Pax6+/− cells efficiently re-epithelialized corneal wounds in vivo but had mild slowing of healing migration compared to the wild-type. Cells aligned parallel to quartz grooves in vitro, but the Pax6+/− cells were less robustly oriented than the wild-type. In the reconstructed corneal culture system, corneal epithelial cells continued to migrate radially, showing that the cells are guided by contact-mediated cues from the basement membrane. Recombining wild-type and Pax6 mutant corneal epithelial cells with wild-type and Pax6 mutant corneal stroma showed that normal Pax6 dosage was required autonomously in the epithelial cells for directed migration. Integrin-mediated attachment to the substrate, and intracellular PI3Kγ activity, were required for migration. Pharmacological inhibition of cAMP signaling randomized migration tracks in reconstructed corneas. Conclusions Striking patterns of centripetal migration of corneal epithelial cells observed in vivo are
Röck, Daniel; Wude, Johanna; Yoeruek, Efdal; Bartz-Schmidt, Karl Ulrich; Röck, Tobias
BACKGROUND This study aimed to investigate factors limiting corneal donation at the University Hospital Tübingen. MATERIAL AND METHODS We retrospectively studied all hospital deaths from January 2012 to December 2015, considering each deceased patient as a potential corneal donor. During this period an ophthalmic resident managed corneal donor procurement on a full-time basis. Various factors limiting corneal donation were examined. RESULTS Among the 3412 deaths, 2937 (86.1%) displayed nonfulfillment of corneal donation. Consent for corneal donation was obtained in 475 cases (13.9%). The mean annual corneal donation rate was 13.9 donors per 100 deaths (range: 11.2-17.8). The leading causes of nonfulfillment of corneal donations were refusal to donate (49.8%, 1698 cases) and medical contraindications (23.6%, 805 cases). After next-of-kin interview of 2173 potential donors (109 potential donors were excluded because of logistical problems), willingness to participate in corneal donation was present in 475 cases (21.9%), whereas in 1698 cases (78.1%) corneal donation was refused. CONCLUSIONS Our study showed refusal to donate is the most important factor limiting corneal donation. It seems that increasing the knowledge of people about corneal donation through public education and media are necessary to address the corneal shortage.
McCabe, Kathryn L.; Kunzevitzky, Noelia J.; Chiswell, Brian P.; Xia, Xin; Goldberg, Jeffrey L.; Lanza, Robert
Aim To generate human embryonic stem cell derived corneal endothelial cells (hESC-CECs) for transplantation in patients with corneal endothelial dystrophies. Materials and Methods Feeder-free hESC-CECs were generated by a directed differentiation protocol. hESC-CECs were characterized by morphology, expression of corneal endothelial markers, and microarray analysis of gene expression. Results hESC-CECs were nearly identical morphologically to primary human corneal endothelial cells, expressed Zona Occludens 1 (ZO-1) and Na+/K+ATPaseα1 (ATPA1) on the apical surface in monolayer culture, and produced the key proteins of Descemet’s membrane, Collagen VIIIα1 and VIIIα2 (COL8A1 and 8A2). Quantitative PCR analysis revealed expression of all corneal endothelial pump transcripts. hESC-CECs were 96% similar to primary human adult CECs by microarray analysis. Conclusion hESC-CECs are morphologically similar, express corneal endothelial cell markers and express a nearly identical complement of genes compared to human adult corneal endothelial cells. hESC-CECs may be a suitable alternative to donor-derived corneal endothelium. PMID:26689688
Twa, Michael D.; Parthasarathy, Srinivasan; Roberts, Cynthia; Mahmoud, Ashraf M.; Raasch, Thomas W.; Bullimore, Mark A.
Purpose The volume and complexity of data produced during videokeratography examinations present a challenge of interpretation. As a consequence, results are often analyzed qualitatively by subjective pattern recognition or reduced to comparisons of summary indices. We describe the application of decision tree induction, an automated machine learning classification method, to discriminate between normal and keratoconic corneal shapes in an objective and quantitative way. We then compared this method with other known classification methods. Methods The corneal surface was modeled with a seventh-order Zernike polynomial for 132 normal eyes of 92 subjects and 112 eyes of 71 subjects diagnosed with keratoconus. A decision tree classifier was induced using the C4.5 algorithm, and its classification performance was compared with the modified Rabinowitz–McDonnell index, Schwiegerling’s Z3 index (Z3), Keratoconus Prediction Index (KPI), KISA%, and Cone Location and Magnitude Index using recommended classification thresholds for each method. We also evaluated the area under the receiver operator characteristic (ROC) curve for each classification method. Results Our decision tree classifier performed equal to or better than the other classifiers tested: accuracy was 92% and the area under the ROC curve was 0.97. Our decision tree classifier reduced the information needed to distinguish between normal and keratoconus eyes using four of 36 Zernike polynomial coefficients. The four surface features selected as classification attributes by the decision tree method were inferior elevation, greater sagittal depth, oblique toricity, and trefoil. Conclusions Automated decision tree classification of corneal shape through Zernike polynomials is an accurate quantitative method of classification that is interpretable and can be generated from any instrument platform capable of raw elevation data output. This method of pattern classification is extendable to other classification
Letafatnejad, Mojgan; Beheshtnejad, Amir Hooshang; Ghaffary, Seyed Reza; Hassanpoor, Narges; Yaseri, Mehdi
Purpose. To evaluate the difference in biomechanical properties between contact lens induced corneal warpage and normal and keratoconic eyes. Method. Prospective observational case control study, where 94 eyes of 47 warpage suspicious and 46 eyes of 23 keratoconic patients were included. Warpage suspected cases were followed until a definite diagnosis was made (warpage, normal, or keratoconus). Results. 44 eyes of 22 patients had contact lens related corneal warpage. 46 eyes of 23 people were diagnosed as nonwarpage normal eyes. 46 eyes of 23 known keratoconus patients were included for comparison. The mean age of the participants was 23.8 ± 3.8 years, and 66.2% of the subjects were female. The demographic and refractive data were not different between warpage and normal groups but were different in the keratoconus group. The biomechanical properties (corneal hysteresis or CH and corneal resistance factor or CRF) were different with the highest value in the warpage group followed by normal and keratoconus groups. CRF was 10.08 ± 1.75, 9.23 ± 1.22, and 7.38 ± 2.14 and CH was 10.21 ± 1.57, 9.59 ± 1.21, and 8.69 ± 2.34 in the warpage, normal, and keratoconus groups, respectively. Conclusion. Corneal biomechanics may be different in people who develop contact lens induced warpage. PMID:27688908
Bignami, Fabio; Lorusso, Anna; Rama, Paolo; Ferrari, Giulio
The aim of this study was to test the efficacy of Neurokinin-1 Receptor (NK-1R) antagonist -Fosaprepitant- in inducing regression of established corneal neovascularization (CNV). Twenty C57BL/6 mice underwent alkali burn. Seven days later, when corneal neovessels had developed, they received Fosaprepitant 10 mg/ml, administered topically six times a day in the right eye for 10 days. In parallel, a group of 20 causticated mice was treated with normal saline, as control. A second independent experiment was also performed (n = 10/group). Finally, ten healthy mice received the same topical treatment for 10 days to evaluate Fosaprepitant safety. Haemangiogenesis and lymphangiogenesis were measured by means of vesselj plugin (imagej). Secondary endpoints, such as leucocyte infiltration, corneal opacity and corneal fluorescein staining were also evaluated. Inflammatory cell composition was assessed by flow cytometry. Differences between groups were assessed using unpaired t-test, Mann-Whitney U-test or two-way anova, as appropriate. Topical Fosaprepitant administration induced a significant reduction of (i) CD31(+) blood corneal neovessels (-27%, p = 0.0132), (ii) LYVE1(+) lymphatic corneal neovessels (-31%, p = 0.0118) and (iii) CD45(+) leucocyte infiltration (-36%; p = 0.0237). The second independent experiment confirmed these data. Moreover, Fosaprepitant-treated corneas showed a reduction in opacity, no impairment in corneal fluorescein staining and decreased infiltration of neutrophils (-72%, p < 0.05) and macrophages (-75%, p < 0.01). Finally, topical Fosaprepitant was not toxic to the ocular surface: no signs of conjunctivitis, opacity, perforations or corneal fluorescein staining were detected. Similarly, corneal TUJ1(+) nerve density was not affected. Our data suggest that NK-1R antagonists, such as Fosaprepitant, could be a new, promising therapeutic tool to inhibit CNV after this has been established. © 2017 Acta Ophthalmologica Scandinavica
Gore, Daniel M; O'Brart, David; French, Paul; Dunsby, Chris; Allan, Bruce D
To measure depth-specific riboflavin concentrations in corneal stroma using two-photon fluorescence microscopy and compare commercially available transepithelial corneal collagen cross-linking (CXL) protocols. Transepithelial CXL riboflavin preparations--MedioCross TE, Ribocross TE, Paracel plus VibeX Xtra, and iontophoresis with Ricrolin+--were applied to the corneal surface of fresh postmortem rabbit eyes in accordance with manufacturers' recommendations for clinical use. Riboflavin 0.1% (VibeX Rapid) was applied after corneal epithelial debridement as a positive control. After riboflavin application, eyes were snap frozen in liquid nitrogen. Corneal cross sections 35-μm thick were cut on a cryostat, mounted on a slide, and imaged by two-photon fluorescence microscopy. Mean (SD) concentrations were calculated from five globes tested for each protocol. Peak riboflavin concentration of 0.09% (± 0.01) was observed within the most superficial stroma (stromal depth 0-10 μm) in positive controls (epithelium-off). At the same depth, peak stromal riboflavin concentrations for MedioCross TE, Ricrolin+, Paracel/Xtra, and Ribocross TE were 0.054% (± 0.01), 0.031% (0.003), 0.021% (± 0.001), and 0.015% (± 0.004), respectively. At a depth of 300 μm (within the demarcation zone commonly seen after corneal cross-linking), the stromal concentration in epithelium-off positive controls was 0.075% (± 0.006), while at the same depth MedioCross TE and Ricrolin+ achieved 0.018% (± 0.006) and 0.016% (0.002), respectively. None of the remaining transepithelial protocols achieved concentrations above 0.005% at this same 300-μm depth. Overall, MedioCross TE was the best-performing transepithelial formulation. Corneal epithelium is a significant barrier to riboflavin absorption into the stroma. Existing commercial transepithelial CXL protocols achieve relatively low riboflavin concentrations in the anterior corneal stroma when compared to gold standard epithelium-off absorption
Bucht, Curry; Söderberg, Per; Manneberg, Göran
The corneal endothelium serves as the posterior barrier of the cornea. Factors such as clarity and refractive properties of the cornea are in direct relationship to the quality of the endothelium. The endothelial cell density is considered the most important morphological factor of the corneal endothelium. Pathological conditions and physical trauma may threaten the endothelial cell density to such an extent that the optical property of the cornea and thus clear eyesight is threatened. Diagnosis of the corneal endothelium through morphometry is an important part of several clinical applications. Morphometry of the corneal endothelium is presently carried out by semi automated analysis of pictures captured by a Clinical Specular Microscope (CSM). Because of the occasional need of operator involvement, this process can be tedious, having a negative impact on sampling size. This study was dedicated to the development and use of fully automated analysis of a very large range of images of the corneal endothelium, captured by CSM, using Fourier analysis. Software was developed in the mathematical programming language Matlab. Pictures of the corneal endothelium, captured by CSM, were read into the analysis software. The software automatically performed digital enhancement of the images, normalizing lights and contrasts. The digitally enhanced images of the corneal endothelium were Fourier transformed, using the fast Fourier transform (FFT) and stored as new images. Tools were developed and applied for identification and analysis of relevant characteristics of the Fourier transformed images. The data obtained from each Fourier transformed image was used to calculate the mean cell density of its corresponding corneal endothelium. The calculation was based on well known diffraction theory. Results in form of estimated cell density of the corneal endothelium were obtained, using fully automated analysis software on 292 images captured by CSM. The cell density obtained by the
Ortega-Usobiaga, Julio; Llovet-Osuna, Fernando; Djodeyre, Mohammad Reza; Llovet-Rausell, Andrea; Beltran, Jaime; Baviera, Julio
To assess the incidence, culture results, and visual outcomes of infectious keratitis after laser in situ keratomileusis (LASIK) and surface ablation when topical moxifloxacin was added to postoperative prophylaxis with tobramycin. Clínica Baviera, Instituto Oftalmológico Europeo, Bilbao, Spain. Retrospective case series review. The medical records of 55 255 patients (108 014 eyes) who had LASIK and surface ablation were reviewed to identify cases of infectious keratitis. The incidence, risk factors, clinical course, days to diagnosis, treatment, and final visual outcomes were recorded. These data were compared with previously published data of 221 437 eyes that received postoperative tobramycin alone. Post-LASIK infectious keratitis was diagnosed in 10 eyes (9 patients) and post-surface ablation infectious keratitis in 11 eyes (10 patients). The onset of infection was early in 40.00% of cases after LASIK and in 36.36% after surface ablation. Cultures were positive in 2 cases after surface ablation. Immediate flap lifting and irrigation with antibiotics were performed in all eyes after LASIK. The final corrected distance visual acuity was 20/20 or better in 7 cases after LASIK (70.00%) and 7 cases after surface ablation (63.64%) and 20/40 or better in all cases after LASIK or surface ablation. The incidence of infectious keratitis decreased from 0.025% to 0.011% (P < .001) per procedure after LASIK and from 0.200% to 0.066% (P < .001) after surface ablation. Infectious keratitis was less frequent after LASIK than after surface ablation. The frequency of infection, mainly early-onset infection, was lower when the postoperative treatment was tobramycin and moxifloxacin rather than tobramycin alone. No author has a financial or proprietary interest in any material or method mentioned. Copyright © 2015 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.
Gürlü, Vuslat Pelitli; Erda, Nazan
To report the acute management and clinical findings of a case of corneal bee sting and to report the outcome of corneal endothelial cell analysis 1 year after trauma. Clinical findings, anterior segment photographs, corneal endothelial images, and medical treatment of a case of right corneal bee sting are presented. Right and left central corneal endothelial cell analysis was performed by noncontact specular microscopy. The stinger was removed from the cornea. Systemic, subconjunctival, and topical steroids and systemic and topical antibiotics were given. One year later, a corneal scar and anterior capsular opacity of the lens in the right eye were shown by slit-lamp examination. Endothelial cell analysis determined that the endothelial cell density of the right eye was substantially decreased compared with the left eye. Corneal infiltration gradually decreased, presumably because of the systemic, topical, and subconjunctival steroids. Late complications observed in this case included a substantial decrease in cornea endothelial cell density, a corneal scar, and anterior capsular opacity.
Park, Young-Woo; Kang, Byung-Jae; Lim, Jae Hyun; Ahn, Jung-Mo; Lim, Hyun Sook
A 13-year-old castrated male Yorkshire terrier developed a corneal ulcer 2 weeks after intracapsular lens extraction (ICLE) in the right eye. The corneal ulcer was treated with levofloxacin eye drops. A plaque with a white luster developed in the central cornea 2 weeks after treatment with levofloxacin eye drops. The corneal plaque was surgically removed under inhalant anesthesia. The corneal plaque displayed antimicrobial activity against Escherichia coli. Furthermore, levofloxacin content in the plaque was confirmed by matrix-assisted laser desorption/ionization time-of-flight/time-of-flight (MALDI-TOF/TOF) mass spectrometry (MS). The corneal ulcer completely resolved 2 weeks after the surgical removal of the corneal lesion and replacement of levofloxacin eye drops with tobramycin eye drops. Although the topical use of levofloxacin is unlikely to lead to corneal chemical deposits due to the high water solubility of the drug compared to other topical fluoroquinolones, this patient developed corneal plaque of the antibiotic drop.
Bourges, J-L; Hubschman, J-P; Burt, B; Culjat, M; Schwartz, S D
Robotic ocular microsurgery including corneal suturing has been proven to be feasible in porcine eyes. To determine whether or not bimanual teleoperated robotic penetrating keratoplasty (PK) can be performed in porcine and human eyes. Three arms of the da Vinci surgical robot were loaded with a dual-channel video and two, 360 degrees -rotating, 8 mm, wrested-end effector instruments and placed over porcine eyes or over a human cadaver head. The surgeon remotely performed mechanical trephination, cardinal sutures, continuous 10.0 nylon sutures and suture adjustments on both eyes. The procedures were documented with still and video photography. Using the da Vinci robot, penetrating keratoplasty procedures were successfully performed on both porcine eyes and human eyes in natural anatomical conditions. The precise placement of continuous sutures was facilitated by the wrested-end forceps. Orbital rims and nose did not limit surgical motions. Teleoperated robotic penetrating keratoplasty is technically feasible in humans. Further studies are pending to implement the procedure with femtosecond laser and other automated steps.
Halberstadt, M; Athmann, S; Hagenah, M
Different methods of corneal cryopreservation have been introduced, those employing intracellular cryoprotectants such as Me2SO or glycerol being the most widely favored. We investigated the influence of several freeze-thaw trauma variables on the survival of porcine endothelial monolayers when employing the extracellular cryoprotective agent dextran. We first examined the effects of various dextran concentrations and then, having ascertained the optimal concentration, further investigated the influence of fetal calf serum (FCS) concentration in the cryopreservation medium, the cooling rate, the thawing temperature, and the length of the preincubation in the freezing medium prior to cryopreservation. The numerical densities of endothelial cells were determined at dissection in hypoosmotic balanced salt solution and after organ culture by staining with alizarin red S and trypan blue. Morphological evaluation was not performed directly after thawing but after a subsequent organ culture at 37 degrees C to detect latent cell damage after freeze-thaw trauma. Our data revealed that corneas cryopreserved in minimal essential medium containing 10% dextran but lacking FCS, preincubated for 3 h, frozen at a cooling rate of 1 degrees C/min, and thawed at 37 degrees C incurred the lowest cell losses (22.4%, SD +/- 3.8). We conclude that dextran is an effective cryoprotectant for freezing of porcine corneas. However, variations between species in the results of cryopreservation require further investigation of an in vivo animal model and studies with human corneas before its clinical use can be recommended.
Piñero, David P; Alcón, Natividad
Biomechanics is often defined as 'mechanics applied to biology'. Due to the variety and complexity of the behaviour of biological structures and materials, biomechanics is better defined as the development, extension and application of mechanics for a better understanding of physiology and physiopathology and consequently for a better diagnosis and treatment of disease and injury. Different methods for the characterisation of corneal biomechanics are reviewed in detail, including those that are currently commercially available (Ocular Response Analyzer and CorVis ST). The clinical applicability of the parameters provided by these devices are discussed, especially in the fields of glaucoma, detection of ectatic disorders and orthokeratology. Likewise, other methods are also reviewed, such as Brillouin microscopy or dynamic optical coherence tomography and others with potential application to clinical practice but not validated for in vivo measurements, such as ultrasonic elastography. Advantages and disadvantages of all these techniques are described. Finally, the concept of biomechanical modelling is revised as well as the requirements for developing biomechanical models, with special emphasis on finite element modelling. © 2014 The Authors. Clinical and Experimental Optometry © 2014 Optometry Australia.
Shiloh, Roni; Munitz, Hanan; Portuguese, Shirley; Gross-Isseroff, Ruth; Sigler, Mayanit; Bodinger, Liron; Katz, Nachum; Stryjer, Rafael; Hermesh, Haggai; Weizman, Abraham
Most data imply that dopaminergic transmission is essential for proper hypothalamic-mediated core temperature regulation. Altered central dopaminergic transmission is suggested to be involved in the pathophysiology of schizophrenia. Thus, hypothetically, schizophrenia patients might be at increased risk of developing thermoregulatory dysregulation manifested by alterations in core temperature, as well as in peripheral tissue, the temperature of which has been shown to correlate with core temperature (e.g. cornea). Previous small pilot studies of ours showed that schizophrenia patients may exhibit corneal temperature abnormalities. Hence, we assessed corneal temperature in a controlled sample of drug-free ( n =11) and medicated ( n =28) schizophrenia patients compared to healthy comparison subjects ( n =9), using a FLIR thermal imaging camera. Drug-free schizophrenia patients exhibited significantly higher corneal temperature compared to healthy subjects, typical antipsychotic drug (APD)-treated patients ( n =16) and atypical APD-treated patients ( n =12) (37.08+/-1.46 degrees C vs. 33.37+/-2.51 degrees C, 31.08+/-1.43 degrees C and 31.67+/-0.44 degrees C respectively, p <0.0001; p <0.001 vs. each group separately). The healthy comparison subjects and the atypical APD-treated patients exhibited comparable corneal temperatures and these two groups exhibited higher corneal temperatures compared to the typical APD-treated patients ( p <0.01 and p =0.051 respectively). In conclusion, this study indicates that drug-free schizophrenia patients exhibit substantially higher corneal temperature compared to healthy comparison subjects or medicated patients, and that APDs may decrease corneal temperature either to normal (atypical APD) or to subnormal (typical APD) values. The relevance of these phenomena to the pathophysiology of schizophrenia, the biological mechanism underlying drug-induced corneal temperature alterations, the possible role of temperature-lowering drugs
Razmjoo, Hassan; Abtahi, Mohammad-Ali; Roomizadeh, Peyman; Mohammadi, Zahra; Abtahi, Seyed-Hossein
Corneal bee sting is an uncommon environmental eye injury that can result in various ocular complications with an etiology of penetrating, immunologic, and toxic effects of the stinger and its injected venom. In this study we present our experience in the management of a middle-aged male with a right-sided deep corneal bee sting. On arrival, the patient was complaining of severe pain, blurry vision with acuity of 160/200, and tearing, which he had experienced soon after the injury. Firstly, we administered conventional drugs for eye injuries, including topical antibiotic, corticosteroid, and cycloplegic agents. After 2 days, corneal stromal infiltration and edema developed around the site of the sting, and visual acuity decreased to 100/200. These conditions led us to remove the stinger surgically. Within 25 days of follow-up, the corneal infiltration decreased gradually, and visual acuity improved to 180/200. We suggest a two-stage management approach for cases of corneal sting. For the first stage, if the stinger is readily accessible or primary dramatic reactions, including infiltration, especially on the visual axis, exist, manual or surgical removal would be indicated. Otherwise, we recommend conventional treatments for eye injuries. Given this situation, patients should be closely monitored for detection of any worsening. If the condition does not resolve or even deteriorates, for the second stage, surgical removal of the stinger under local or generalized anesthesia is indicated.
Stepp, Mary Ann
Integrins were first described just over 20 years ago and have been studied in the cornea by many groups interested in how the cornea functions in health and disease. There are a minimum of 12 different integrin heterodimers reported to be expressed by the major resident cells of the cornea: the corneal and limbal epithelial cells, keratocytes/fibroblasts, and corneal endothelial cells. These different integrin heterodimers play important and varied roles in maintaining the cornea and organizing how its cells interact with their surrounding extracellular matrix to maintain corneal clarity. In this review, an overview of the discovery and functions of integrins is provided along with a description of the current state of our knowledge of this large family of important proteins. While we have learned a lot about corneal integrins over the past 20 years, there is still much to learn. Areas where gaps in our knowledge of integrin functions in the cornea are slowing our progress in understanding corneal diseases and dystrophies at a molecular level are highlighted.
Louis, David N.; Feldman, Michael; Carter, Alexis B.; Dighe, Anand S.; Pfeifer, John D.; Bry, Lynn; Almeida, Jonas S.; Saltz, Joel; Braun, Jonathan; Tomaszewski, John E.; Gilbertson, John R.; Sinard, John H.; Gerber, Georg K.; Galli, Stephen J.; Golden, Jeffrey A.; Becich, Michael J.
Context We define the scope and needs within the new discipline of computational pathology, a discipline critical to the future of both the practice of pathology and, more broadly, medical practice in general. Objective To define the scope and needs of computational pathology. Data Sources A meeting was convened in Boston, Massachusetts, in July 2014 prior to the annual Association of Pathology Chairs meeting, and it was attended by a variety of pathologists, including individuals highly invested in pathology informatics as well as chairs of pathology departments. Conclusions The meeting made recommendations to promote computational pathology, including clearly defining the field and articulating its value propositions; asserting that the value propositions for health care systems must include means to incorporate robust computational approaches to implement data-driven methods that aid in guiding individual and population health care; leveraging computational pathology as a center for data interpretation in modern health care systems; stating that realizing the value proposition will require working with institutional administrations, other departments, and pathology colleagues; declaring that a robust pipeline should be fostered that trains and develops future computational pathologists, for those with both pathology and non-pathology backgrounds; and deciding that computational pathology should serve as a hub for data-related research in health care systems. The dissemination of these recommendations to pathology and bioinformatics departments should help facilitate the development of computational pathology. PMID:26098131
... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Corneal electrode. 886.1220 Section 886.1220 Food... DEVICES OPHTHALMIC DEVICES Diagnostic Devices § 886.1220 Corneal electrode. (a) Identification. A corneal electrode is an AC-powered device, usually part of a special contact lens, intended to be applied directly...
... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Corneal electrode. 886.1220 Section 886.1220 Food... DEVICES OPHTHALMIC DEVICES Diagnostic Devices § 886.1220 Corneal electrode. (a) Identification. A corneal electrode is an AC-powered device, usually part of a special contact lens, intended to be applied directly...
... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Corneal electrode. 886.1220 Section 886.1220 Food... DEVICES OPHTHALMIC DEVICES Diagnostic Devices § 886.1220 Corneal electrode. (a) Identification. A corneal electrode is an AC-powered device, usually part of a special contact lens, intended to be applied directly...
... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Corneal electrode. 886.1220 Section 886.1220 Food... DEVICES OPHTHALMIC DEVICES Diagnostic Devices § 886.1220 Corneal electrode. (a) Identification. A corneal electrode is an AC-powered device, usually part of a special contact lens, intended to be applied directly...
... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Corneal electrode. 886.1220 Section 886.1220 Food... DEVICES OPHTHALMIC DEVICES Diagnostic Devices § 886.1220 Corneal electrode. (a) Identification. A corneal electrode is an AC-powered device, usually part of a special contact lens, intended to be applied directly...
Wang, Liqiang; Shankarappa, Sahadev A.; Tong, Rong; Ciolino, Joseph B.; Tsui, Jonathan H.; Chiang, Homer H.; Kohane, Daniel S.
Purpose Ocular local anesthetics (OLA’s) currently used in routine clinical practice for corneal anesthesia are short acting and their ability to delay corneal healing makes them unsuitable for long-term use. In this study, we examined the effect on the duration of corneal anesthesia of the site-1 sodium channel blocker tetrodotoxin (TTX), applied with either proparacaine or the chemical permeation enhancer OTAB. The effect of test solutions on corneal healing was also studied. Methods Solutions of TTX, proparacaine, and OTAB, singly or in combination were applied topically to the rat cornea. The blink response, an indirect measure of corneal sensitivity, was recorded using a Cochet-Bonnet esthesiometer, and the duration of corneal anesthesia calculated. The effect of test compounds on the rate of corneal epithelialization was studied in vivo following corneal debridement. Results Combination of TTX and proparacaine resulted in corneal anesthesia that was 8–10 times longer in duration than that from either drug administered alone, while OTAB did not prolong anesthesia. The rate of corneal healing was moderately delayed following co-administration of TTX and proparacaine. Conclusion Co-administration of TTX and proparacaine significantly prolonged corneal anesthesia but in view of delayed corneal re-epithelialization, caution is suggested in use of the combination. PMID:23615270
Abdelfattah, Nizar Saleh; Amgad, Mohamed; Zayed, Amira A.; Hussein, Heba; Abd El-Baky, Nawal
The cornea is maintained in an avascular state by maintaining an environment whereby anti-angiogenic factors take the upper hand over factors promoting angiogenesis. Many of the common pathologies affecting the cornea involve the disruption of such equilibrium and the shift towards new vessel formation, leading to corneal opacity and eventually-vision loss. Therefore it is of paramount importance that the molecular underpinnings of corneal neovascularization (CNV) be clearly understood, in order to develop better targeted treatments. This article is a review of the literature on the recent discoveries regarding pro-angiogenic factors of the cornea (such as vascular endothelial growth factors, fibroblast growth factor and matrix metalloproteinases) and anti-angiogenic factors of the cornea (such as endostatins and neostatins). Further, we review the molecular underpinnings of lymphangiogenesis, a process now known to be almost separate from (yet related to) hemangiogenesis. PMID:27275438
Fukuda, Ken; Chikama, Tai-ichiro; Takahashi, Mutsuo; Nishida, Teruo
To report a case of bilateral idiopathic corneal keloid. Retrospective review of clinical features, histopathological findings, clinical management, and outcome. A 2-year-old boy with bilateral corneal keloid was treated with lamellar keratoplasty and tranilast eye drops. Peripheral localized white corneal nodules had been present bilaterally since the age of approximately 6 months in the absence of any history of trauma, inflammatory disease, or relevant family history. Pathological examination of the excised corneal buttons revealed myofibroblast proliferation (positive staining for α-smooth muscle actins), a haphazard arrangement of collagen bundles, and the absence of inflammatory cells. On the basis of these findings, a diagnosis of corneal keloid was assigned. The size of the corneal lesion in the right eye decreased in response to therapy with tranilast eye drops. Lamellar keratoplasty resulted in improved bilateral visual acuity, which was maintained at the 12-year follow-up. This report describes a very rare case of bilateral corneal keloid in the absence of trauma or inflammation that was diagnosed by histological and immunohistochemical examination and electron microscopy. Good visual acuity was maintained over an extended period of postsurgery follow-up. Tranilast may represent a novel adjuvant therapy for corneal keloid.
Badial, Peres R; Cisneros-Àlvarez, Luis Emiliano; Brandão, Cláudia Valéria S; Ranzani, José Joaquim T; Tomaz, Mayana A R V; Machado, Vania M; Borges, Alexandre S
The aim of this study was to compare ocular dimensions, corneal curvature, and corneal thickness between horses affected with hereditary equine regional dermal asthenia (HERDA) and unaffected horses. Five HERDA-affected quarter horses and five healthy control quarter horses were used. Schirmer's tear test, tonometry, and corneal diameter measurements were performed in both eyes of all horses prior to ophthalmologic examinations. Ultrasonic pachymetry was performed to measure the central, temporal, nasal, dorsal, and ventral corneal thicknesses in all horses. B-mode ultrasound scanning was performed on both eyes of each horse to determine the dimensions of the ocular structures and to calculate the corneal curvature. Each corneal region examined in this study was thinner in the affected group compared with the healthy control group. However, significant differences in corneal thickness were only observed for the central and dorsal regions. HERDA-affected horses exhibited significant increases in corneal curvature and corneal diameter compared with unaffected animals. The ophthalmologic examinations revealed mild corneal opacity in one eye of one affected horse and in both eyes of three affected horses. No significant between-group differences were observed for Schirmer's tear test, intraocular pressure, or ocular dimensions. Hereditary equine regional dermal asthenia-affected horses exhibit decreased corneal thickness in several regions of the cornea, increased corneal curvature, increased corneal diameter, and mild corneal opacity. Additional research is required to determine whether the increased corneal curvature significantly impacts the visual accuracy of horses with HERDA. © 2014 American College of Veterinary Ophthalmologists.
Maharana, Prafulla K; Sharma, Namrata; Vajpayee, Rasik B
Acute corneal hydrops is a condition characterized by stromal edema due to leakage of aqueous through a tear in descemet membrane. The patient presents with sudden onset decrease in vision, photophobia, and pain. Corneal thinning and ectasias combined with trivial trauma to the eye mostly by eye rubbing is considered as the underlying cause. With conservative approach self-resolution takes around 2 to 3 months. Surgical intervention is required in cases of non-resolution of corneal edema to avoid complications and for early visual rehabilitation. Intracameral injection of air or gas such as perflouropropane is the most common surgical procedure done. Recent investigative modality such as anterior segment optical coherence tomography is an extremely useful tool for diagnosis, surgical planning, and postoperative follow up. Resolution of hydrops may improve the contact lens tolerance and visual acuity but most cases require keratoplasty for visual rehabilitation. PMID:23925338
Qazi, Yureeda; Hamrah, Pedram
Corneal transplantation is the most commonly performed organ transplantation. Immune privilege of the cornea is widely recognized, partly because of the relatively favorable outcome of corneal grafts. The first-time recipient of corneal allografts in an avascular, low-risk setting can expect a 90% success rate without systemic immunosuppressive agents and histocompatibility matching. However, immunologic rejection remains the major cause of graft failure, particularly in patients with a high risk for rejection. Corticosteroids remain the first-line therapy for the prevention and treatment of immune rejection. However, current pharmacological measures are limited in their side-effect profiles, repeated application, lack of targeted response, and short duration of action. Experimental ocular gene therapy may thus present new horizons in immunomodulation. From efficient viral vectors to sustainable alternative splicing, we discuss the progress of gene therapy in promoting graft survival and postulate further avenues for gene-mediated prevention of allogeneic graft rejection. PMID:24138037
Aicher, Sue A; Hegarty, Deborah M; Hermes, Sam M
Corneal pain is mediated by primary afferent fibers projecting to the dorsal horn of the medulla, specifically the trigeminal nucleus caudalis. In contrast to reflex responses, the conscious perception of pain requires transmission of neural activity to higher brain centers. Ascending pain transmission is mediated primarily by pathways to either the thalamus or parabrachial nuclei. We previously showed that some corneal afferent fibers preferentially contact parabrachial-projecting neurons in the rostral pole of the trigeminal nucleus caudalis, but the role of these projection neurons in transmitting noxious information from the cornea has not been established. In the present study, we show that noxious stimulation of the corneal surface activates neurons in the rostral pole of the nucleus caudalis, including parabrachially projecting neurons that receive direct input from corneal afferent fibers. We used immunocytochemical detection of c-Fos protein as an index of neuronal activation after noxious ocular stimulation. Animals had previously received injections of a retrograde tracer into either thalamic or parabrachial nuclei to identify projection neurons in the trigeminal dorsal horn. Noxious stimulation of the cornea induced c-Fos in neurons sending projections to parabrachial nuclei, but not thalamic nuclei. We also confirmed that corneal afferent fibers identified with cholera toxin B preferentially target trigeminal dorsal horn neurons projecting to the parabrachial nucleus. The parabrachial region sends ascending projections to brain regions involved in emotional and homeostatic responses. Activation of the ascending parabrachial system may explain the extraordinary salience of stimulation of corneal nociceptors. Copyright © 2014 Elsevier B.V. All rights reserved.
Felipe; Gonzalez; Gallar; Belmonte
The number and immunocytochemical characteristics of trigeminal ganglion neurons providing sensory innervation to the cornea were studied in the mouse. Corneal neurons were retrogradely labelled with fluorogold placed on the cornea after removal of the epithelium with n-heptanol. Corneal neurons were counted, sized and characterized immunocytochemically with antisera against substance P (SP), calcitonin gene-related peptide (CGRP), calbindin, calretinin, and with a monoclonal antibody (RT97) against neurofilament proteins. A total of 258 corneal neurons were counted, most of them located in the ophthalmic division of the trigeminal ganglion. They represent only a small fraction (1.3%) of the population of trigeminal ganglion neurons. More than 70% of corneal neurons were classified as 'small dark' according to their cell body area and the absence of immunoreactivity to RT97. A low percentage of corneal neurons, usually large in size, contained calcium binding proteins. Fifty-eight percent of the corneal neurons were immunoreactive to CGRP, and 20% to SP. Corneal wounding with NaOH, which affects stromal nerve trunk, did not modify the total number of corneal neurons or their neuropeptide content. However, this increased the total number of calbindin-positive and decreased the RT97-positive neurons. Thus, unlike in other nociceptive neurons, peripheral axotomy did not modify the SP/CGRP content of corneal neurons.Trigeminal ganglion neurons projecting to the cornea are similar in size and neuropeptide content to nociceptive neurons of other territories. Their number is high in relation to the corneal surface, thus confirming that the cornea has a large nociceptive representation in the trigeminal ganglion. Copyright 1999 European Federation of Chapters of the International Association for the Study of Pain.
Knappe, S; Stachs, O; Guthoff, R
Wearing orthokeratology contact lenses (OCL, Hecht-see free; Hecht, Germany) overnight can change corneal refraction by up to -4.5 dioptre (dpt) based on corneal adaptation to the double reverse surface of the OCL. This allows a temporary independence on glasses or contact lenses. It is known that the central corneal thickness decreases while the corneal thickness in the periphery probably increases. The aim of this study was to investigate the corneal changes of volunteers wearing OCL with in vivo confocal microscopy. Five young adults (mean 22.8 years, three female, two male) with low to moderate myopia (range -1.75 to -3.5 dpt; sphere equivalent -2.7+/-0.59 dpt) were fitted with OCL of reverse-geometry design in both eyes. Lenses were worn in both eyes overnight and were removed immediately in the morning. The volunteers were examined with in vivo confocal microscopy using a combination of Heidelberg retina tomograph II and the Rostock cornea module before wearing the OCL and after the 1(st), 3(rd), 5(th), 7(th), 13(th), 20(th) and 25(th) nights. The central and mid-peripheral total corneal thickness as well as the epithelial thickness were examined in the morning between 7.30 am and 9.30 am. The central and the mid-peripheral epithelial corneal thickness was reduced significantly (p<0.05) from day 1 to the 13(th) day. This stabilized later until the the examination was concluded. No significant changes (p>0.05) were found in the central or mid-peripheral total corneal thickness after 25 days of wearing the OCL. Wearing OCL leads to a reduction in the central corneal epithelial thickness. Our inability to find an increase in mid-peripheral total and epithelial corneal thickness may be because the expected increase of the mid-peripheral cornea is limited to a defined area, which makes repeated measurements at a particular point difficult.
Lai, Jui-Yang; Cheng, Hsiao-Yun; Ma, David Hui-Kang
Hyaluronic acid (HA) is a linear polysaccharide naturally found in the eye and therefore is one of the most promising biomaterials for corneal endothelial regenerative medicine. This study reports, for the first time, the development of overrun-processed porous HA hydrogels for corneal endothelial cell (CEC) sheet transplantation and tissue engineering applications. The hydrogel carriers were characterized to examine their structures and functions. Evaluations of carbodiimide cross-linked air-dried and freeze-dried HA samples were conducted simultaneously for comparison. The results indicated that during the fabrication of freeze-dried HA discs, a technique of introducing gas bubbles in the aqueous biopolymer solutions can be used to enlarge pore structure and prevent dense surface skin formation. Among all the groups studied, the overrun-processed porous HA carriers show the greatest biological stability, the highest freezable water content and glucose permeability, and the minimized adverse effects on ionic pump function of rabbit CECs. After transfer and attachment of bioengineered CEC sheets to the overrun-processed HA hydrogel carriers, the therapeutic efficacy of cell/biopolymer constructs was tested using a rabbit model with corneal endothelial dysfunction. Clinical observations including slit-lamp biomicroscopy, specular microscopy, and corneal thickness measurements showed that the construct implants can regenerate corneal endothelium and restore corneal transparency at 4 weeks postoperatively. Our findings suggest that cell sheet transplantation using overrun-processed porous HA hydrogels offers a new way to reconstruct the posterior corneal surface and improve endothelial tissue function. PMID:26296087
Brunette, Isabelle; Sherknies, Denis; Terry, Mark A; Chagnon, Miguel; Bourges, Jean-Louis; Meunier, Jean
To characterize the 3-D corneal shape deformation incurred by Fuchs corneal dystrophy and pseudophakic bullous keratopathy by using the integrated analysis of Orbscan (Bausch & Lomb Surgical, Rochester, NY) topographic maps of affected and normal corneas. One hundred thirty-seven patients with Fuchs dystrophy or pseudophakic keratopathy were divided into three groups according to the severity of the disease: mild (central corneal thickness [CCT], 500-710 μm; n = 46); moderate (710-775 μm; n = 45), and severe (775-1100 μm; n = 46). A control group included 411 normal subjects matched for age and refractive spherical equivalent (three control subjects for each subject with Fuchs or pseudophakic keratopathy). The four groups were compared by using 3-D corneal shape atlases illustrating mean anterior elevation, posterior elevation, and pachymetry. Whereas the atlases showed little anterior surface deformation, the posterior surface presented a significant central bulging toward the anterior chamber. The thinnest point was displaced away from the center, toward the superior nasal midperiphery. The corneal periphery remained relatively unaffected by the disease, except in the final stage. 3-D atlases provided detailed new information on the 3-D corneal shape deformation incurred by Fuchs corneal dystrophy throughout disease progression.
Hjortdal, Jesper; Ivarsen, Anders
Corneal refractive surgery aims to reduce or eliminate refractive errors of the eye by changing the refractive power of the cornea. For the last 20 years controlled excimer laser ablation of corneal tissue, either directly from the corneal stromal surface or from the corneal interior after creation of a superficial corneal flap has become widely used to correct myopia, hyperopia, and astigmatism. Recently, an intrastromal refractive procedure whereby a tissue lenticule is cut free in the corneal stroma by a femtosecond laser and removed through a small peripheral incision has been introduced. This procedure avoids creation of a corneal flap and the potential associated risks while avoiding the slow visual recovery of surface ablation procedures. Precise intrastromal femtosecond laser cutting of the fine lenticule requires very controlled laser energy delivery in order to avoid lenticule irregularities, which would compromise the refractive result and visual acuity. This newly introduced all-femtosecond based flap-free intracorneal refractive procedure has been documented to be a predictable, efficient, and safe procedure for correction of myopia and astigmatism. Technological developments related to further improved cutting quality, hyperopic and individualized treatments are desirable.
Moffatt, S Louise; Cartwright, Victoria A; Stumpf, Thomas H
Abstract One hundred years ago, on 7 December 1905, Dr Eduard Zirm performed the world's first successful human corneal transplant. This significant milestone was achieved only after many decades of unsuccessful trial and error; however, it did not lead to relatively 'routine' keratoplasty success for several more decades. The idea of replacing an opaque cornea had been suggested for centuries, and had stimulated theoretical approaches to the problem by many esteemed physicians throughout history. However, little practical progress was made in the ultimate realization of the dream until the 19th century when pioneering surgeons pursued extensive studies in relation to both animal and human 'keratoplasty'. Clinical progress and scientific insight developed slowly, and it was ultimately due to parallel advances in medicine such as anaesthesia and antisepsis that Zirm's success was finally achieved. Key concepts were enshrined such as the use of fresh tissue from the same species, careful placement and handling of tissue, and the development of specialized instrumentation such as the circular trephine. In the latter half of the 20th century, many 'masters' of corneal surgery evolved significant refinements in technique and instrumentation with the development of corticosteroids, antibiotics, surgical microscopes, improved trephines, viscoelastics and suture materials, that enable this delicate procedure to be routinely performed with the prospect of success. There are still limitations to corneal transplantation, and corneal allograft rejection still poses the greatest challenge to the modern corneal surgeon. In the foreseeable future it may be in the laboratory, rather than the theatre, that further milestones will be achieved. This review aims to highlight the significant milestones in the rich history of corneal transplantation, and to pay tribute to the many inspired and dedicated individuals involved in the development of keratoplasty to a point where the
Bosnar, Damir; Dekaris, Iva; Gabrić, Nikica; Markotić, Alemka; Lazić, Ratimir; Špoljarić, Ninoslav
Aim To determine pro-inflammatory cytokine secretion from human corneas with different pathology and to establish whether cytokine profile influences corneal graft outcome. Method Secretion of both proinflammatory cytokine interleukin (IL)-1α and tumor necrosis factor (TNF)-α was measured after cultivation of 47 corneas collected from corneal graft recipients suffering from different corneal diseases. Non-inflammatory corneal diseases were keratoconus (n = 8), keratoglobus (n = 2), bullous keratopathy (n = 11), and Groenouw stromal dystrophy type II (n = 2), whereas inflammatory included vascularized corneal scar (n = 14), rejected graft (n = 6), and corneal ulcer (n = 4). Corneas were cultivated at 37°C for 24 hours and frozen until cytokine detection was measured by immunoassay. Donor corneas unsuitable for transplantation were used as controls (n = 7). Corneal graft recipients were followed at least 18 months and rejection rate was calculated for each group. Results The median concentration of IL-1α secreted from corneas of recipients with non-inflammatory diseases was 2.47 pg/mm3 (range, 0.13-9.95). In inflammatory corneal diseases, IL-1α concentration was significantly higher (median, 5.92 pg/mm3; range, 0.48-12.68; P = 0.005). IL-1α production in controls (median, 0.63 pg/mm3; range, 0.36-1.29 pg/mm3) was significantly lower than in inflammatory corneal diseases (P<0.001) and non-inflammatory diseases (P = 0.008). Low level of TNF-α was detected only in 5 cases of vascularized corneal scars, 3 cases of bullous keratopathy, and 3 cases of graft rejection. Rejection rate was significantly higher in inflammatory than in non-inflammatory group (46% vs <10%, respectively, P = 0.008). IL-1α and TNF-α were absent from all patient’s sera, confirming its local intra-ocular production. Conclusion Increased production of IL-1α in corneal recipients with inflammatory diseases suggests its role in corneal graft
Mrochen, Michael; Jankov, Mirko; Bueeler, Michael; Seiler, Theo
Purpose: Corneal topography data expressed as corneal aberrations are frequently used to report corneal laser surgery results. However, the optical image quality at the retina depends on all optical elements of the eye such as the human lens. Thus, the aim of this study was to investigate the correlations between the corneal and total wavefront aberrations and to discuss the importance of corneal aberrations for representing corneal laser surgery results. Methods: Thirty three eyes of 22 myopic subjects were measured with a corneal topography system and a Tschernig-type wavefront analyzer after the pupils were dilated to at least 6 mm in diameter. All measurements were centered with respect to the line of sight. Corneal and total wavefront aberrations were calculated up to the 6th Zernike order in the same reference plane. Results: Statistically significant correlations (p < 0.05) between the corneal and total wavefront aberrations were found for the astigmatism (C3,C5) and all 3rd Zernike order coefficients such as coma (C7,C8). No statistically significant correlations were found for all 4th to 6th order Zernike coefficients except for the 5th order horizontal coma C18 (p equals 0.003). On average, all Zernike coefficients for the corneal aberrations were found to be larger compared to Zernike coefficients for the total wavefront aberrations. Conclusions: Corneal aberrations are only of limited use for representing the optical quality of the human eye after corneal laser surgery. This is due to the lack of correlation between corneal and total wavefront aberrations in most of the higher order aberrations. Besides this, the data present in this study yield towards an aberration balancing between corneal aberrations and the optical elements within the eye that reduces the aberration from the cornea by a certain degree. Consequently, ideal customized ablations have to take both, corneal and total wavefront aberrations, into consideration.
Ljubimov, Alexander V.; Saghizadeh, Mehrnoosh
Corneal wound healing is a complex process involving cell death, migration, proliferation, differentiation, and extracellular matrix remodeling. Many similarities are observed in the healing processes of corneal epithelial, stromal and endothelial cells, as well as cell-specific differences. Corneal epithelial healing largely depends on limbal stem cells and remodeling of the basement membrane. During stromal healing, keratocytes get transformed to motile and contractile myofibroblasts largely due to activation of transforming growth factor-β system. Endothelial cells heal mostly by migration and spreading, with cell proliferation playing a secondary role. In the last decade, many aspects of wound healing process in different parts of the cornea have been elucidated, and some new therapeutic approaches have emerged. The concept of limbal stem cells received rigorous experimental corroboration, with new markers uncovered and new treatment options including gene and microRNA therapy tested in experimental systems. Transplantation of limbal stem cell-enriched cultures for efficient re-epithelialization in stem cell deficiency and corneal injuries has become reality in clinical setting. Mediators and course of events during stromal healing have been detailed, and new treatment regimens including gene (decorin) and stem cell therapy for excessive healing have been designed. This is a very important advance given the popularity of various refractive surgeries entailing stromal wound healing. Successful surgical ways of replacing the diseased endothelium have been clinically tested, and new approaches to accelerate endothelial healing and suppress endothelial-mesenchymal transformation have been proposed including Rho kinase (ROCK) inhibitor eye drops and gene therapy to activate TGF-β inhibitor SMAD7. Promising new technologies with potential for corneal wound healing manipulation including microRNA, induced pluripotent stem cells to generate corneal epithelium, and
Yoder, Paul R.; Macri, Timothy F.; Telfair, William B.; Bennett, Peter S.; Martin, Clifford A.; Warner, John W.
We describe a new electro-optical device being developed to provide precise measurements of the three-dimensional topography of the human cornea. This device, called a digital keratoscope, is intended primarily for use in preparing for and determining the effect of corneal surgery procedures such as laser refractive keratectomy, radial keratotomy or corneal transplant on the refractive power of the cornea. It also may serve as an aid in prescribing contact lenses. The basic design features of the hardware and of the associated computer software are discussed, the means for alignment and calibration are described and typical results are given.
Machowicz-Matejko, Eulalia; Rakowska, Ewa; Zagórski, Zbigniew
To present therapeutic application of tectonic epikeratoplasty as logical patch in severe ocular surface disorders. Full thickness corneo-scleral transplants, 14 mm in diameter were used in 67 operations of 41 patients with corneal perforation or descemetocele. (14 women and 27 men), in the period 1998-2008. The mean age of patients was 55.2 +/- 17.7 years (range 15-82). The transplants were sutured over the limbus or the scleral rim and was implanted under the conjunctiva after 360 degrees peritomy. Donor tissue unsuitable for penetrating keratoplasty because of poor endothelium or corneal scarring, was obtained from Lublin Eye Bank. We observed closing of the perforation in all cases. Healing of the ulceration with scar formation and new vessels ingrowth was noted. In some eyes repeated epikeratoplasties were performed. Tectonic epikeratoplasty is a safe and simple method of treatment of corneal perforations. It provides a biological patch stimulating the healing of corneal defects. It gives time for systemic treatment before further ocular surface reconstructive procedures can be performed.
Hazra, Sarbani; Nandi, Sudip; Naskar, Deboki; Guha, Rajdeep; Chowdhury, Sushovan; Pradhan, Nirparaj; Kundu, Subhas C; Konar, Aditya
Successful repair of a damaged corneal surface is a great challenge and may require the use of a scaffold that supports cell growth and differentiation. Amniotic membrane is currently used for this purpose, in spite of its limitations. A thin transparent silk fibroin film from non-mulberry Antheraea mylitta (Am) has been developed which offers to be a promising alternative. The silk scaffolds provide sufficient rigidity for easy handling, the scaffolds support the sprouting, migration, attachment and growth of epithelial cells and keratocytes from rat corneal explants; the cells form a cell sheet, preserve their phenotypes, express cytokeratin3 and vimentin respectively. The films also support growth of limbal stem cell evidenced by expression of ABCG2. The cell growth on the silk film and the amniotic membrane is comparable. The implanted film within the rabbit cornea remains transparent, stable. The clinical examination as well as histology shows absence of any inflammatory response or neovascularization. The corneal surface integrity is maintained; tear formation, intraocular pressure and electroretinography of implanted eyes show no adverse changes. The silk fibroin film from non-mulberry silk worms may be a worthy candidate for use as a corneal scaffold.
Jiang, Yan; Fu, Wei-Cai; Zhang, Lin
To explore mechanism of nduction of fibroblast to corneal endothelial cell. Rabbit conjunctiva fibroblasts were used as feeder cells, rabbit oral mucosa epithelial cells were used as seed cells, and human denuded amniotic membrane was used as carrier to establish tissue engineering corneal endothelium. The transformation effect was observed. As concentration of mitomycin C increased, cell survival rate gradually decreased, cell proliferation was obviously inhibited when concentration≥25 μg/mL; 5 days after being treated by 5 μg/mL mitomycin C, cell body was enlarged and extended without cell fusion, however after being treated by 0.5 μg/mL mitomycin C, cell body was significantly proliferated and gradually fused; after 3 weeks of culture, stratified epithelium appeared on rabbit oral mucosa epithelial cells, differentiation layers were 4-5 and were well differentiated, the morphology was similar to corneal endothelial cells; Under electron microscope, surface layer of cells were polygonal, tightly connected to another with microvilli on the border, there was hemidesmosome between basal cells and human denuded amniotic membrane. Fibroblast cells have the potential of multi-directional differentiation, effective induction can promote emergence of intercellular desmosomes between seed cells and emergence of epithelial surface microvilli, and differentiate to the corneal endothelial cell. However, clinical application still needs more research and safety evaluation. Copyright © 2014 Hainan Medical College. Published by Elsevier B.V. All rights reserved.
Hazra, Sarbani; Nandi, Sudip; Naskar, Deboki; Guha, Rajdeep; Chowdhury, Sushovan; Pradhan, Nirparaj; Kundu, Subhas C.; Konar, Aditya
Purpose: Successful repair of a damaged corneal surface is a great challenge and may require the use of a scaffold that supports cell growth and differentiation. Amniotic membrane is currently used for this purpose, in spite of its limitations. A thin transparent silk fibroin film from non-mulberry Antheraea mylitta (Am) has been developed which offers to be a promising alternative. The silk scaffolds provide sufficient rigidity for easy handling, the scaffolds support the sprouting, migration, attachment and growth of epithelial cells and keratocytes from rat corneal explants; the cells form a cell sheet, preserve their phenotypes, express cytokeratin3 and vimentin respectively. The films also support growth of limbal stem cell evidenced by expression of ABCG2. The cell growth on the silk film and the amniotic membrane is comparable. The implanted film within the rabbit cornea remains transparent, stable. The clinical examination as well as histology shows absence of any inflammatory response or neovascularization. The corneal surface integrity is maintained; tear formation, intraocular pressure and electroretinography of implanted eyes show no adverse changes. The silk fibroin film from non-mulberry silk worms may be a worthy candidate for use as a corneal scaffold. PMID:26908015
Kasprzak, Henryk T.; Jaronski, Jaroslaw W.
Paper presents results of in vivo measurements of dynamic variations of the corneal topography by use of the Twyman Green interferometer. Sequence of interferograms were recorded by the CCD camera and stored in the computer memory. Then the fringe tracking method was used separately to each interferogram giving the phase surface of the wave reflected from the cornea in the numerical form. Results from neighboring interferograms were subtracted giving new sequence of changes of the corneal topography within 40 ms. Obtained results show the complex space distribution of the corneal topography variations.
Wahl, Christina; Li, Tong; Choden, Tsering; Howland, Howard
In this study we wish to augment our understanding of the effect of environment on corneal growth and morphology. To understand how corneal development of chicks raised in constant light differs from that of ‘normal’ eyes exposed to cyclic periods of light and dark, white Leghorn chicks were raised under either constant light (approximately 700 lux at cage top) or in 12 h light/12 h dark conditions for up to 12 weeks after hatching. To determine whether corneal expansion is uniform, some birds from each group received corneal tattoos for periodic photographic assessment. By 16 days of age, constant light corneas weighed less than light/dark regimen corneas [7.39 ± 0.35 mg (SE) vs. 8.47 mg ± 0.26 mg SE wet weight, P ≤ 0.05], and corresponding differences were seen in corneal dry weights. Spatial expansion of the corneal surface was uniform in both groups, but the rate of expansion was slower in constant light chicks [0.0327 ± 0.009 (SE) vs. 0.144 ± 0.018 (SE) mm2 day−1 for normal chicks, P ≤ 0.001]. At 1 day of age, there were 422 ± 12.5 (SE) stromal cells 0.01 mm−2 in the central cornea and 393 ± 21.5 (SE) stromal cells 0.01 mm−2peripherally. Although this difference is not statistically significant, the cell densities in the central cornea were always larger than those of the peripheral cornea in all eight measurements over a 10.5-week period, and this difference is significant (P ≤ 0.008, binomial test). Light/dark regimen birds show no such consistent difference in cell densities between central and peripheral corneas. Thus, the density distribution of corneal stromal cells of chicks grown in constant light differs from that of normal chicks. Taken together, all these observations suggest that diurnal cycles of light and darkness are necessary for normal corneal growth. PMID:19245502
Veréb, Zoltán; Póliska, Szilárd; Albert, Réka; Olstad, Ole Kristoffer; Boratkó, Anita; Csortos, Csilla; Moe, Morten C.; Facskó, Andrea; Petrovski, Goran
Corneal tissue regeneration is of crucial importance for maintaining normal vision. We aimed to isolate and cultivate human corneal stroma-derived mesenchymal stem-like cells (CSMSCs) from the central part of cadaver corneas and study their phenotype, multipotency, role in immunity and wound healing. The isolated cells grew as monolayers in vitro, expressed mesenchymal- and stemness-related surface markers (CD73, CD90, CD105, CD140b), and were negative for hematopoietic markers as determined by flow cytometry. CSMSCs were able to differentiate in vitro into fat, bone and cartilage. Their gene expression profile was closer to bone marrow-derived MSCs (BMMSCs) than to limbal epithelial stem cells (LESC) as determined by high-throughput screening. The immunosuppressive properties of CSMSCs were confirmed by a mixed lymphocyte reaction (MLR), while they could inhibit proliferation of activated immune cells. Treatment of CSMSCs by pro-inflammatory cytokines and toll-like receptor ligands significantly increased the secreted interleukin-6 (IL-6), interleukin-8 (IL-8) and C-X-C motif chemokine 10 (CXCL-10) levels, as well as the cell surface adhesion molecules. CSMSCs were capable of closing a wound in vitro under different stimuli. These cells thus contribute to corneal tissue homeostasis and play an immunomodulatory and regenerative role with possible implications in future cell therapies for treating sight-threatening corneal diseases. PMID:27195722
Gkika, Maria; Labiris, Georgios; Giarmoukakis, Athanassios; Koutsogianni, Anna; Kozobolis, Vassilios
To evaluate corneal hysteresis (CH) and corneal resistance factor (CRF) in keratoconic (KC) eyes before and after corneal collagen cross-linking (CXL). Furthermore, to determine potential correlations with a series of corneal and demographic factors. The study consisted of 50 KC eyes that underwent CXL. CH and CRF were measured by the ocular response analyzer (ORA). Correlations were attempted with uncorrected visual acuity (UVA), best spectacle-corrected visual acuity (BSCVA), central corneal thickness (CCT), mean keratometry (Km), astigmatism (Astig.), residual astigmatism, age, and gender. Fifty non-KC eyes served as controls. CH and CRF (mean ± SD) for non-KC eyes were 10.1 ± 1.9 mmHg and 9.7 ± 2.4 mmHg respectively, while for KC eyes preoperatively they were 8.2 ± 1.4 mmHg (p = 0.007) and 7.4 ± 2.3 mmHg (p = 0.01) respectively. Non-significant differences were detected between preoperative and postoperative CH and CRF measurements in KC eyes (p = 0.518 and p = 0.479 respectively). Significant correlations were found between ORA parameters and BSCVA, CCT, Km, Astig. and residual astigmatism. ORA parameters demonstrate significant differences between KC and non-KC eyes. Both CH and CRF present significant correlations with visual acuity and corneal parameters. CXL exerts a non-significant impact on ORA measurements.
Tomás-Juan, Javier; Murueta-Goyena Larrañaga, Ane; Hanneken, Ludger
Photorefractive keratectomy (PRK) remodels corneal stroma to compensate refractive errors. The removal of epithelium and the ablation of stroma provoke the disruption of corneal nerves and a release of several peptides from tears, epithelium, stroma and nerves. A myriad of cytokines, growth factors, and matrix metalloproteases participate in the process of corneal wound healing. Their balance will determine if reepithelization and stromal remodeling are appropriate. The final aim is to achieve corneal transparency for restoring corneal function, and a proper visual quality. Therefore, wound-healing response is critical for a successful refractive surgery. Our goal is to provide an overview into how corneal wounding develops following PRK. We will also review the influence of intraoperative application of mitomycin C, bandage contact lenses, anti-inflammatory and other drugs in preventing corneal haze and post-PRK pain. PMID:25444646
Coster, Douglas J
Corneal transplantation is a triumph of modern ophthalmology. The possibility of corneal transplantation was first raised in 1797 but a century passed before Zirm achieved the first successful penetrating graft in 1905. Gibson reported the first corneal graft in Australia from Brisbane in 1940 and English established the first eye bank there a few years later. Corneal transplantation evolved steadily over the twentieth century. In the second half of the century, developments in microsurgery, including surgical materials such as monofilament nylon and strong topical steroid drops, accounted for improvements in outcomes. In 2013, approximately 1500 corneal transplants were done in Australia. Eye banking has evolved to cope with the rising demands for donor corneas. Australian corneal surgeons collaborated to establish and support the Australian Corneal Graft Registry in 1985. It follows the outcomes of their surgery and has become an important international resource for surgeons seeking further improvement with the procedure.
Tomás-Juan, Javier; Murueta-Goyena Larrañaga, Ane; Hanneken, Ludger
Photorefractive keratectomy (PRK) remodels corneal stroma to compensate refractive errors. The removal of epithelium and the ablation of stroma provoke the disruption of corneal nerves and a release of several peptides from tears, epithelium, stroma and nerves. A myriad of cytokines, growth factors, and matrix metalloproteases participate in the process of corneal wound healing. Their balance will determine if reepithelization and stromal remodeling are appropriate. The final aim is to achieve corneal transparency for restoring corneal function, and a proper visual quality. Therefore, wound-healing response is critical for a successful refractive surgery. Our goal is to provide an overview into how corneal wounding develops following PRK. We will also review the influence of intraoperative application of mitomycin C, bandage contact lenses, anti-inflammatory and other drugs in preventing corneal haze and post-PRK pain.
Georgeon, Cristina; Andreiuolo, Felipe; Borderie, Marie; Ghoubay, Djida; Rault, Josette; Borderie, Vincent M.
Purpose: To search for gold-standard histology indicators using alternative imaging modalities in keratoconic corneas. Methods: Prospective observational case–control study. Fourteen keratoconic corneas and 20 normal corneas (10 in vivo healthy subjects and 10 ex vivo donor corneas) were examined. Images of corneas were taken by spectral domain optical coherence tomography (SD-OCT) and in vivo confocal microscopy (IVCM) before keratoplasty. The same removed corneal buttons were imaged after keratoplasty with full-field optical coherence microscopy (FFOCM) and then fixed and sent for histology. Controls consisted of normal subjects imaged in vivo with IVCM and donor corneas imaged ex vivo with FFOCM. Corneal structural changes related to pathology were noted with each imaging modality. Cell density was quantified by manual cell counting. Results: Keratoconus indicators (ie, epithelial thinning/thickening, cell shape changes, ferritin deposits, basement membrane anomalies, Bowman layer thinning, ruptures, interruptions, scarring, stromal modifications, and appearance of Vogt striae) were generally visible with all modalities. Additional features could be seen with FFOCM in comparison with gold-standard histology, particularly in the Bowman layer region, whereas the combination of SD-OCT plus IVCM detected 76% of those features detected in histology. Three-dimensional FFOCM imaging aided interpretation of two-dimensional IVCM and SD-OCT data. Basal epithelial cell and keratocyte densities were significantly lower in patients with keratoconus than those in normals (P < 0.0001). Conclusions: Structural and cellular assessment of the keratoconic cornea by means of either in vivo SD-OCT combined with IVCM or ex vivo FFOCM in both cross-sectional and en face views can detect as many keratoconus indicators as gold-standard histology. PMID:27560027
Queirós, António; Villa-Collar, César; Jorge, Jorge; Gutiérrez, Ángel Ramón; González-Méijome, José Manuel
Background To analyse the asphericity of the anterior corneal surface (ACS) for different diameters, and correlate those values with corneal higher order aberrations (cHOA) before and after myopic treatments with corneal refractive therapy (CRT) for orthokeratology and customized (CL) and standard laser (SL) assisted in situ keratomileusis (LASIK). Setting Clínica Oftalmológica NovoVisión, Madrid, Spain. Methods The right eyes of 81 patients (27 in each treatment group), with a mean age of 29.94 ± 7.5 years, were analysed. Corneal videokeratographic data were used to obtain corneal asphericity (Q) for different corneal diameters from 3 to 8 mm and cHOA root mean square (RMS) obtained from Zernike polynomials for a pupil diameter of 6 mm. Results There were statistically significant differences in asphericity values calculated at different corneal diameters for different refractive treatments and their changes. The difference between asphericity at 3 and 8 mm reference diameters showed statistically significant correlations with spherical-like cHOA that was also significantly increased after all procedures. Conclusions The shift in corneal asphericity and the differences among different treatment techniques are more evident for the smaller reference diameters. These differences can be much reduced or even masked for a peripheral reference point at 4 mm from centre, which is used by some corneal topographers.
Li, Xinyu; Zhou, Qinbo; Hanus, Jakub; Anderson, Chastain; Zhang, Hongmei; Dellinger, Michael; Brekken, Rolf; Wang, Shusheng
Neovascularization (NV) in the cornea is a major cause of vision impairment and corneal blindness. Hemangiogenesis and lymphangiogenesis induced by inflammation underlie the pathogenesis of corneal NV. The current mainstay treatment, corticosteroid, treats the inflammation associated with corneal NV, but is not satisfactory due to such side effects as cataract and the increase in intraocular pressure. It is imperative to develop a novel therapy that specifically targets the hemangiogenesis, lymphangiogenesis and inflammation pathways underlying corneal NV. Histone deacetylase inhibitors (HDACi) have been in clinical trials for cancer and other diseases. In particular, HDACi suberoylanilide hydroxamic acid (SAHA, vorinostat, Zolinza) has been approved by the FDA for the treatment of cutaneous T-cell lymphoma. The functional mechanism of SAHA in cancer and especially in corneal NV remains unclear. Here, we show that topical application of SAHA inhibits neovascularization in an alkali-burn corneal injury model. Mechanistically, SAHA inhibits corneal NV by repressing hemangiogenesis, inflammation pathways and previously overlooked lymphangiogenesis. Topical SAHA is well tolerated on the ocular surface. In addition, the potency of SAHA in corneal NV appears to be comparable to the current steroid therapy. SAHA may possess promising therapeutic potential in alkali-burn corneal injury and other inflammatory neovascularization disorders. PMID:23186311
Peat, Frances J; Kawcak, Christopher E
The current understanding of pathology as it relates to common diseases of the equine musculoskeletal system is reviewed. Conditions are organized under the fundamental categories of developmental, exercise-induced, infectious, and miscellaneous pathology. The overview of developmental pathology incorporates the new classification system of juvenile osteochondral conditions. Discussion of exercise-induced pathology emphasizes increased understanding of the contribution of cumulative microdamage caused by repetitive cyclic loading. Miscellaneous musculoskeletal pathology focuses on laminitis, which current knowledge indicates should be regarded as a clinical syndrome with a variety of possible distinct mechanisms of structural failure that are outlined in this overview. Copyright © 2015 Elsevier Inc. All rights reserved.
Tummanapalli, Shyam Sunder; Potluri, Haresh; Vaddavalli, Pravin Krishna; Sangwan, Virender S
To investigate and compare the efficacy of axial and tangential corneal topography maps obtained using the Orbscan IIz scanning-slit device to distinguish differences in eyes with subclinical keratoconus from normal eyes. LV Prasad Eye Institute, Hyderabad, India. Retrospective cross-sectional study. Axial and tangential maps of the anterior and posterior corneal surfaces were obtained in eyes of patients with subclinical keratoconus (normal fellow eye of an eye with clinically diagnosed keratoconus). The following measurements were obtained from each map and compared between the 2 groups: location of the corneal apex in millimeters relative to the corneal vertex, dioptric power at the corneal apex and corneal vertex, corneal irregularity indices at 3.0 mm and 5.0 mm, anterior-posterior apex ratio, and inferior-superior dioptric asymmetry value. Maps were obtained in 71 eyes (71 patients) with subclinical keratoconus and 76 normal eyes (76 patients). The tangential posterior apex curvature was significantly steeper than the axial posterior apex curvature in both groups (P < .001). The anterior-posterior apex ratio on the tangential map demonstrated the highest area under the receiver operating characteristic (ROC) curve of 0.992 (cutoff ≥-6.97, sensitivity 98.6%, specificity 98.7%) followed by the posterior irregularity index in the 5.0 mm zone with an area under the ROC curve of 0.938 (cutoff ≥0.4, sensitivity 98.6%, specificity 84.2%) in differentiating subclinical keratoconus eyes from normal eyes. The anterior-posterior apex ratio on the tangential map and 5.0 mm irregularity index of the posterior corneal surface were highly sensitive and specific for early detection of subclinical keratoconus. Tangential corneal topography maps should be considered in preoperative subclinical keratoconus screening. No author has a financial or proprietary interest in any material or method mentioned. Copyright © 2015 ASCRS and ESCRS. Published by Elsevier Inc. All rights
Anderson, S B; de Souza, R Ferreira; Hofmann-Rummelt, C; Seitz, B
Background/aims: Amniotic membrane transplantation (AMT) has become well established as a treatment for chronic epithelial defects, conjunctival reconstruction, and partial limbal cell deficiency. The aim of this study was to describe cases of corneal calcification following AMT and to search for risk factors that might predispose to this unusual finding. Methods: Details of 117 AMTs on 93 corneas of 91 patients with a follow up period of at least 1 month performed since 1999 were collected prospectively. In those with calcification clinical photographs were studied and the medical records retrospectively examined. Results: 15 calcifications in 117 AMTs (12.8%) were identified, occurring 3–17 (median 6.1) weeks after AMT, during a follow up period of 4–151 (median 25) weeks. Overall epithelial healing rate was 83%. Calcification covered a surface area between 0.7–40.5 mm2 maximum size with varied morphology. The primary diagnosis was diverse. Risk factors included the use of phosphate eye drops and pre-existing calcification in the operative or other eye. No patient with a “patch” AMT developed calcification. Conclusions: Corneal calcification occurs after some cases of AMT. A common risk factor was the postoperative use of phosphate containing eye drops. PMID:12714401
Hollander, E; Buchalter, A J; DeCaria, C M
With increasing access to gambling facilities through casinos, the Internet, and other venues, PG is a rapidly emerging mental health concern. This impulse-control disorder tends to be comorbid with a wide range of other disorders and is reportedly associated with a high rate of suicide. For most gamblers, gambling is a form of entertainment, but for many individuals, the activity leads to far-reaching disruption of family and work. The personal and societal financial ramifications are severe, and many individuals with PG end up in the criminal justice system. An understanding of the neurobiology of PG is beginning to surface. 5-HT is linked to behavioral initiation and disinhibition, which are important in the onset of the gambling cycle and the difficulty in ceasing the behavior. Norepinephrine is associated with the arousal and risk taking in patients with PG. Dopamine is linked to positive and negative reward, the addictive component of this disorder. Effective treatment strategies for pathological gamblers are emerging. Potentially useful pharmacologic agents include SRIs (clomipramine and fluvoxamine), mood stabilizers for pathological gamblers with comorbid bipolar disorders (lithium), and naltrexone. Cognitive-behavioral psychotherapies offer promising results in the treatment of patients with this disorder. To devise prevention and early-intervention programs, research is needed to identify specific features of the individuals at risk for gambling problems. Education targeting vulnerable youth that show early signs of gambling behavior may be worthwhile and should be investigated further. Funding is necessary to support these endeavors, so perhaps a portion of tax revenues generated from the gambling industry should go toward specialized treatment facilities, educational efforts, and research into the neurobiology and treatment of PG.
Hanlon, Samuel D.; Behzad, Ali R.; Sakai, Lynn Y.; Burns, Alan R.
Elastic tissue was first described well over a hundred years ago and has since been identified in nearly every part of the body. In this review, we examine elastic tissue in the corneal stroma with some mention of other ocular structures which have been more thoroughly described in the past. True elastic fibers consist of an elastin core surrounded by fibrillin microfibrils. However, the presence of elastin fibers is not a requirement and some elastic tissue is comprised of non-elastin-containing bundles of microfibrils. Fibers containing a higher relative amount of elastin are associated with greater elasticity and those without elastin, with structural support. Recently it has been shown that the microfibrils, not only serve mechanical roles, but are also involved in cell signaling through force transduction and the release of TGF-β. A well characterized example of elastin-free microfibril bundles (EFMBs) is found in the ciliary zonules which suspend the crystalline lens in the eye. Through contraction of the ciliary muscle they exert enough force to reshape the lens and thereby change its focal point. It is believed that the molecules comprising these fibers do not turn-over and yet retain their tensile strength for the life of the animal. The mechanical properties of the cornea (strength, elasticity, resiliency) would suggest that EFMBs are present there as well. However, many authors have reported that, although present during embryonic and early postnatal development, EFMBs are generally not present in adults. Serial-block-face imaging with a scanning electron microscope enabled 3D reconstruction of elements in murine corneas. Among these elements were found fibers that formed an extensive network throughout the cornea. In single sections these fibers appeared as electron dense patches. Transmission electron microscopy provided additional detail of these patches and showed them to be composed of fibrils (∼10nm diameter). Immunogold evidence clearly
Berthaut, Alexandre; Mirshahi, Pezhman; Benabbou, Nadia; Azzazene, Dalel; Bordu, Camille; Therwath, Amu; Legeais, Jean-marc
Purpose Mechanisms by which fibroblast networks between stromal lamellae are laid in the corneal stroma are far from clear. We have investigated the role of vascular endothelial growth factor receptors (VEGFRs) by in vitro studies in the human corneal network formation obtained from donors whose ages ranged from 19 to 89 years. Methods Corneal fibroblasts were prepared from cornea donations. The functional properties of these cells to form networks were analyzed using a semi solid matrix (substratum) of Matrigel™. The presence of VEGF receptor-1 (VEGFR-1) and the functionality in these fibroblasts were investigated using immunofluorescence, molecular analysis (gene microarray, reverse transcription polymerase chain reaction [RT–PCR] and VEGFR siRNA transfections), and cell culture. Results Corneal fibroblasts from 61 donors were classified into two groups according to whether they formed (82%) a reticulum on Matrigel™ or not (18%). By RT–PCR and immunofluorescence analysis, we showed that corneal fibroblasts expressed VEGFR-1 (mRNA and protein). Further, cell culture analysis revealed that only the network (reticulum) forming corneal fibroblast expressed VEGFR-1 in contrast to non network-forming fibroblasts. Use of inhibitors such as VEGFR-1 siRNA transfection or neutralizing antibody (Avastin™) indicated that VEGFR-1 was essential to the formation of the corneal network in vitro. Conclusions The cell reticulum formation seemed to be directly related to the expression of VEGFR-1 in the corneal fibroblast, and this expression decreased with age. The decrease in VEGFR-1 expression is probably related to the diminution of autocrine functions, which may alter the overall tissular homeostasis. This may culminate in the gradual development of poor vision, which is observed in certain pathologies and in aging individuals. PMID:19816604
Tang, Emily W H; Law, Ricky W K; Lai, Jimmy S M
We report a case of crystalline keratopathy caused by Alocasia macrorrhiza. The diagnosis was made based on the observation of needle-like crystals in the corneal stroma following injury to that eye. The condition resolved in 3 months with the disappearance of the crystals confirmed by follow-up confocal microscopy.
Singh, Rahul S; Tewari, Priyamvada; Bourges, Jean Louis; Hubschman, Jean Pierre; Bennett, David B; Taylor, Zachary D; Lee, H; Brown, Elliott R; Grundfest, Warren S; Culjat, Martin O
An indicator of ocular health is the hydrodyanmics of the cornea. Many corneal disorders deteriorate sight as they upset the normal hydrodynamics of the cornea. The mechanisms include the loss of endothelial pump function of corneal dystophies, swelling and immune response of corneal graft rejection, and inflammation and edema, which accompany trauma, burn, and irritation events. Due to high sensitivity to changes of water content in materials, a reflective terahertz (300 GHz and 3 THz) imaging system could be an ideal tool to measure the hydration level of the cornea. This paper presents the application of THz technology to visualize the hydration content across ex vivo porcine corneas. The corneas, with a thickness variation from 470 - 940 µm, were successfully imaged using a reflective pulsed THz imaging system, with a maximum SNR of 50 dB. To our knowledge, no prior studies have reported on the use of THz in measuring hydration in corneal tissues or other ocular tissues. These preliminary findings indicate that THz can be used to accurately sense hydration levels in the cornea using a pulsed, reflective THz imaging system.
corneal collagen as a treatment for keratoconus (1) indicating that it is a safe photosensitizer. The maximum percent inhibition using RF and blue light...Seiler (2003) Riboflavin/ultraviolet-a-induced collagen crosslinking for the treatment of keratoconus . Am J Ophthalmol, 135, 620-7. 2. Fujisato, T
blue light. RF-5P with UVA irradiation has recently been used to crosslink corneal collagen as a treatment for keratoconus (2). Thus, RF-5P appears...induced collagen crosslinking for the treatment of keratoconus . American journal of ophthalmology. 2003 May;135(5):620-7. 3. McCall AS, Kraft S
Purpose: To evaluate the biomechanics of corneal ring implants by providing a related mathematical theory and biomechanical model for the treatment of myopia and keratoconus. Methods: The spherical dome model considers the inhomogeneity of the tunica of the eye, dimensions of the cornea, lamellar structure of the corneal stroma, and asphericity of the cornea. It is used in this study for calculating a strengthening factor sf for the characterization of different ring-shaped corneal implant designs. The strengthening factor is a measure of the amount of strengthening of the cornea induced by the implant. Results: For ring segments and incomplete rings, sf = 1.0, which indicates that these implants are not able to strengthen the cornea. The intracorneal continuous complete ring (MyoRing) has a strengthening factor of up to sf = 3.2. The MyoRing is, therefore, able to strengthen the cornea significantly. Conclusions: The result of the presented biomechanical analysis of different ring-shaped corneal implant designs can explain the different postoperative clinical results of different implant types in myopia and keratoconus. PMID:26312619
In order to develop new therapeutic modalities for corneal diseases, it is essential to combine cutting-edge translational research based upon liberal original ideas obtained from clinical experience with state-of-the-art basic science and technology. Here, I describe seven important research projects on which our group has been working. 1. Elucidation of the pathogenesis in gelatinous drop-like corneal dystrophy(GDLD). Due to loss of function of the tumor-associated calcium signal transducer 2 (TACSTD2), a responsible gene for this dystrophy, tight-junction-related proteins cease to function, resulting in severe corneal epithelial barrier impairment. As a result, various proteins contained in tear fluid continuously penetrate into the corneal stroma, promoting the development of massive amyloid deposits. 2. The development of cultivated mucosal epithelial transplantation: A landmark surgery, involving the transplantation of cultivated mucosal epithelial cells from in vitro to in vivo, now recognized as the next generation of ocular surface reconstruction. We began performing cultivated allocorneal epithelial transplantations in 1999, and cultivated auto-corneal and auto-oral mucosal epithelial transplantations in 2002. These proved to be very effective in the reconstruction of both the corneal surface and the conjunctival fornix. 3. Elucidation of the pathogenesis of Stevens-Johnson syndrome: Studies have shown that there is a close relationship between corneal epithelial stem cell loss and the associated degree of visual impairment. We discovered that a steroid pulse therapy at the acute phase aimed at minimizing stem cell loss is very effective in restoring visual acuity. This implies that inhibition of the cytokine storm is essential for the treatment of acute-phase Stevens-Johnson syndrome. The innate immunity abnormality seems to be heavily involved at the onset of this devastating disease. 4. Elucidation of the involvement of EP3 and toll like receptor 3
Mastropasqua, Leonardo; Massaro-Giordano, Giacomina; Nubile, Mario; Sacchetti, Marta
Neurotrophic keratitis (NK) is a rare degenerative disease of the cornea caused by trigeminal nerve damage, which leads to loss of corneal sensitivity, corneal epithelium breakdown, and poor healing. Though extremely uncommon, NK is increasingly recognized for its characteristics as a distinct and well-defined clinical entity rather than a rare complication of various diseases that can disrupt trigeminal innervation. Indeed, the defining feature of NK is loss of corneal sensitivity, and its clinical findings do not correlate with the wide range of systemic or ocular conditions that underlie trigeminal nerve damage. Despite increasing awareness of NK as a distinct condition, its management continues to be challenged by the lack of treatments that target nerve regeneration. This review focuses on the role of corneal nerves in maintaining ocular surface homeostasis, the consequences (such as alterations in neuromediators and corneal cell morphology/function) of impaired innervation, and advances in NK diagnosis and management. Novel therapeutic strategies should aim to improve corneal innervation in order support corneal renewal and healing. J. Cell. Physiol. 232: 717-724, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.
Sun, Yan; Pearlman, Eric
Purpose To investigate the role of the TLR4/MD-2 antagonist eritoran tetrasodium in a murine model of contact lens–associated corneal infiltrates. Methods C57BL/6 mouse corneas were abraded and treated with eritoran tetrasodium or placebo, either before or after stimulation with either LPS, the TLR2 ligand Pam3Cys, or antibiotic-killed Pseudomonas aeruginosa. A 2-mm punch from a silicon hydrogel contact lens was used to cover the corneal surface throughout the inhibition and stimulation period. Corneal infiltrates were detected by in vivo confocal microscopy and by immunohistochemistry for neutrophils. The effect of eritoran tetrasodium on stimulated human corneal epithelial cells (HCECs), macrophages, and neutrophils was also assessed. Results Eritoran tetrasodium significantly inhibited CXC chemokine production in the cornea and development of corneal infiltrates, specifically neutrophils, in response to stimulation with LPS (TLR4), but not Pam3Cys (TLR2). When the antagonist was applied after LPS stimulation, neutrophil infiltration was also inhibited, although a higher concentration was needed. Furthermore, IL-8 production by TLR4- but not TLR2-stimulated HCECs, macrophages and neutrophils was also significantly reduced. Corneal inflammation induced by P. aeruginosa in the presence of tobramycin was found to be dependent on expression of TLR4 and MD-2 and is inhibited by eritoran tetrasodium. Conclusions Eritoran tetrasodium is a highly effective antagonist of TLR4/MD-2-dependent corneal inflammation. PMID:18936141
Ha, Hyo Shin; Song, Kye Yong; Kim, Jae Chan
The purpose of this study is to characterize and compare the ultrastructural changes occurring during the in vivo cultivation of corneal epithelium on amniotic membrane (AM) at several different time points. Corneal burn patients (n=7) with a corneal epithelial defect and severe limbal damage were selected. Initially, AM transplantation with limbal autograft was performed at the acute stage of corneal burn to reconstruct the damaged ocular surface. One to six (mean interval; 3.3+/-1.2) months later, the central part of AM containing an in vivo expanded corneal epithelium was excised and retransplanted in adjacent lesions. The excised epithelium with AM was examined by electron microscopy and immunohistochemical study. By electron microscopy, one and two months after expansion, cultivated epithelium on AM showed an undifferentiated epithelium and an incomplete basement membrane (BM). But, after three months, the cultivated epithelium began to differentiate into a multilayered epithelium with a continuous BM with increased hemidesmosomes. These findings were further confirmed by immunohistochemical study, that cytokeratin K3 was expressed in the cultivated corneal epithelium and newly formed BM was partially positive of collagen IV at three months. At least 3 months may be needed for the proliferation and differentiation of in vivo cultivated corneal epithelium on AM.
Luengo Gimeno, Federico; Lavigne, Victoria; Gatto, Silvia; Croxatto, J Oscar; Correa, Laura; Gallo, Juan E
To evaluate the efficacy of autologous corneal epithelial sheet implantation in restoring transparency of rabbit corneas severely injured by alkaline and the effect of photocoagulation in arresting corneal neovessel ingrowth. Ophthalmology Department, School of Biomedical Sciences, Universidad Austral, Buenos Aires, Argentina. Limbal stem-cell deficiency (LSCD) was induced in 14 rabbits by alkali burns. A limbal cell biopsy was done in the contralateral eye, and the cells were cultured on a fibroblast feeder layer grown on autologous clotted platelet-poor plasma or commercial fibrin for 21 days. Anterior keratectomy was followed by suturing corneal cell sheets over the stroma. If regrowth of vessels occurred, argon laser photocoagulation was applied to them. Rabbits were killed at 30, 60, 90, 180, and 360 days and the corneas processed for histopathology and inmunohistochemistry. A small (2.5 mm(2)) limbal biopsy achieved stem-cell replication in vitro. Corneal clarity and epithelial defects evolved with a trend toward improvement. There was a significant reduction in corneal neovascularization. Histology showed a multilayered stratified epithelium including several epithelial-like cells with clear cytoplasm in the deepest part. There were no signs of intraepithelial mucin cells on the implanted corneas. Immunohistochemical results showed expression of cytokeratins 3 and 12 in the central corneal epithelium and an absence of cytokeratin 19. Autologous limbal epithelial cell transplantation improved the corneal surface in eyes with LSCD. Photocoagulation of neovessel ingrowth was effective over the 1-year follow-up. Results may facilitate the application of this technique in patients.
Slettedal, Jon Klokk; Ringvold, Amund
To examine the relationship between human corneal and environmental temperature. An infrared camera was used to measure the corneal surface temperature in a group of healthy volunteers as well as in an experimental setting with donor corneas and an artificial anterior chamber, employing circulating saline at +37°C. Liquid nitrogen was used to obtain a very low temperature in the experimental setting. High ambient temperature measurements were performed in a sauna. In healthy volunteers, the cornea required at least 20-30 min to adapt to change in ambient temperature. The relationship between corneal and external temperature was relatively linear. At the two extremes, +83°C and -40°C, the corneal temperature was +42°C and +25.1°C, respectively. In the experimental setting, corneal temperature was +24.3°C at air temperature -40°C. A rather stable aqueous humour temperature of +37°C and high thermal conductivity of the corneal tissue prevent corneal frostbite even at extremely low ambient temperatures. © 2015 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.
Ha, Hyo Shin; Song, Kye Yong
The purpose of this study is to characterize and compare the ultrastructural changes occurring during the in vivo cultivation of corneal epithelium on amniotic membrane (AM) at several different time points. Corneal burn patients (n=7) with a corneal epithelial defect and severe limbal damage were selected. Initially, AM transplantation with limbal autograft was performed at the acute stage of corneal burn to reconstruct the damaged ocular surface. One to six (mean interval; 3.3±1.2) months later, the central part of AM containing an in vivo expanded corneal epithelium was excised and retransplanted in adjacent lesions. The excised epithelium with AM was examined by electron microscopy and immunohistochemical study. By electron microscopy, one and two months after expansion, cultivated epithelium on AM showed an undifferentiated epithelium and an incomplete basement membrane (BM). But, after three months, the cultivated epithelium began to differentiate into a multilayered epithelium with a continuous BM with increased hemidesmosomes. These findings were further confirmed by immunohistochemical study, that cytokeratin K3 was expressed in the cultivated corneal epithelium and newly formed BM was partially positive of collagen IV at three months. At least 3 months may be needed for the proliferation and differentiation of in vivo cultivated corneal epithelium on AM. PMID:16778403
Asher, Roy; Gefen, Amit; Moisseiev, Elad; Varssano, David
Patient-specific biomechanical properties of the human cornea are rarely used with finite elements analysis. In order for that to be possible, a proper formulation for biomechanical properties that is based on patient-specific measurable values must be used. In this study, we propose a formula that simulates hyperelastic stress-strain curves based on non-invasive clinical measurements that can be acquired in vivo. These consist of, but are not limited to, center corneal thickness and center corneal curvature as well as corneal resistance factor and applanation diameter that are measured during non-contact tonometry. The presented formulation was demonstrated and validated through several computer simulations. First, mean values that were reported in literature were inputted into the formula to simulate a curve that represents a healthy case. This case was compared to two independent in vitro studies. Then, a sensitivity analysis was carried to identify inputs that have the most dominant effect. Finally, a finite element analysis simulating elevations in intraocular pressure was conducted; the corneal model comprised of patient-specific corneal geometry that was measured in vivo in our clinic as well as the current formulation for patient-specific corneal biomechanics. "Strong" and "weak" corneal tissue cases were simulated and deformations as well as instantaneous curvature optical maps were derived. Results for the simulated healthy curve showed good agreement with the in vitro studies. The sensitivity analysis found the corneal resistance factor and applanation diameter to have the most dominant influence. The finite element analysis of strong and weak biomechanical properties resulted in corneal deformations and instantaneous curvature optical maps that are common for healthy and pathological conditions respectively. In conclusion, the presented modeling technique can be used to assess corneal biomechanics in vivo and therefor may enhance follow-up on the
Carvalho, Luis A.; Tonissi, S. A.; Castro, Jarbas C.
We have developed a novel instrument for computerized corneal topography during surgery. The instrument measures a region of approximately 7 mm in diameter, providing the surgeon with precise values of power and astigmatism. The system is based on a Placido Disc projecting system, which is attached to the objective lens of the surgical microscope. The Placido Disc pattern is reflected by a 50% beam splitter attached to the body of the microscope. At the beam splitter we installed our home-made adaptor and a CCD monochromatic high resolution camera. A high quality frame grabber is installed on a PC and images are digitized at a 480x640 resolution. Algorithms based on image processing techniques were implemented for edge detection of pattern. Calibrating curves based on 4 spherical surfaces were generated and approximately 3600 points were calculated for each exam. Preliminary measurements on 10 healthy corneas were compared with the measurements made on an EyeSys Corneal Topographer. Mean deviation was 0.05 for radius of curvature, 0.24 D for power and 5 degrees for cylinder. This system, with some improvements, may be successfully used to diminish high post surgical astigmatisms in surgeries such as cataract and corneal transplant. This system could also be used to gather preoperative data in corneal topography assisted LASIK.
Manns, Fabrice; Borja, David; Parel, Jean-Marie A.
Purpose. The purpose of this study was to develop a model to predict the corneal temperature and shrinkage during laser thermokeratoplasty and other clinical procedures relying on laser-induced thermal shrinkage of collagenous tissue. Methods. The corneal temperature was calculated by solving the bio-heat equation during laser irradiation using a semi-analytical technique. To calculate shrinkage, we assumed that corneal thermal shrinkage is a thermal denaturation process that follows an Arrhenius equation, and that shrinkage resulting from denaturation is proportional to the amount of thermal damage. We calculated shrinkage for pulsed Ho:YAG laser thermokeratoplasty using the clinical treatment algorithm. Results. The thermal model predicts that the corneal temperature reaches values that may be high enough to induce surface vaporization of the epithelium and thermal damage of the endothelium. Shrinkage calculations show that significant shrinkage is produced only after the third laser pulse. Shrinkage is produced mainly during laser pulses and stops shortly after the start of the cooling phase between laser pulses. Conclusions. These calculations demonstrate that thermal shrinkage can be predicted by combining an optical-thermal model and a thermal denaturation model. Accurate quantitative prediction of the shrinkage effect requires a better knowledge of the dynamics of shrinkage and of the optical thermal response of the cornea.
Crotti, C.; Deloison, F.; Peyrot, D. A.; Savoldelli, M.; Legeais, J.-M.; Roger, F.; Plamann, K.
Femtosecond laser surgery in the volume of corneal tissue is difficult in the case of oedematous or pathological corneas: in those corneas, the propagation of the laser beam is perturbed by the optical scattering. This phenomenon can be greatly reduced by using a better suited laser wavelength. A series of ex vivo surgical experiments has been conducted at wavelengths around 1600 nm. The results have been compared to experiments performed at 800 nm and 1000 nm. We have compared penetration depth and incision quality as a function of wavelength and energy.
Oliva, Matthew S; Schottman, Tim; Gulati, Manoj
Corneal diseases represent the second leading cause of blindness in most developing world countries. Worldwide, major investments in public health infrastructure and primary eye care services have built a strong foundation for preventing future corneal blindness. However, there are an estimated 4.9 million bilaterally corneal blind persons worldwide who could potentially have their sight restored through corneal transplantation. Traditionally, barriers to increased corneal transplantation have been daunting, with limited tissue availability and lack of trained corneal surgeons making widespread keratoplasty services cost prohibitive and logistically unfeasible. The ascendancy of cataract surgical rates and more robust eye care infrastructure of several Asian and African countries now provide a solid base from which to dramatically expand corneal transplantation rates. India emerges as a clear global priority as it has the world's largest corneal blind population and strong infrastructural readiness to rapidly scale its keratoplasty numbers. Technological modernization of the eye bank infrastructure must follow suit. Two key factors are the development of professional eye bank managers and the establishment of Hospital Cornea Recovery Programs. Recent adaptation of these modern eye banking models in India have led to corresponding high growth rates in the procurement of transplantable tissues, improved utilization rates, operating efficiency realization, and increased financial sustainability. The widespread adaptation of lamellar keratoplasty techniques also holds promise to improve corneal transplant success rates. The global ophthalmic community is now poised to scale up widespread access to corneal transplantation to meet the needs of the millions who are currently blind. PMID:22944753
Oliva, Matthew S; Schottman, Tim; Gulati, Manoj
Corneal diseases represent the second leading cause of blindness in most developing world countries. Worldwide, major investments in public health infrastructure and primary eye care services have built a strong foundation for preventing future corneal blindness. However, there are an estimated 4.9 million bilaterally corneal blind persons worldwide who could potentially have their sight restored through corneal transplantation. Traditionally, barriers to increased corneal transplantation have been daunting, with limited tissue availability and lack of trained corneal surgeons making widespread keratoplasty services cost prohibitive and logistically unfeasible. The ascendancy of cataract surgical rates and more robust eye care infrastructure of several Asian and African countries now provide a solid base from which to dramatically expand corneal transplantation rates. India emerges as a clear global priority as it has the world's largest corneal blind population and strong infrastructural readiness to rapidly scale its keratoplasty numbers. Technological modernization of the eye bank infrastructure must follow suit. Two key factors are the development of professional eye bank managers and the establishment of Hospital Cornea Recovery Programs. Recent adaptation of these modern eye banking models in India have led to corresponding high growth rates in the procurement of transplantable tissues, improved utilization rates, operating efficiency realization, and increased financial sustainability. The widespread adaptation of lamellar keratoplasty techniques also holds promise to improve corneal transplant success rates. The global ophthalmic community is now poised to scale up widespread access to corneal transplantation to meet the needs of the millions who are currently blind.
Royer, D.J.; Carr, D.J.J.
Type 1 interferons (IFNα/β) mediate immunologic host resistance to numerous viral infections including herpes simplex virus type 1 (HSV-1). The pathways responsible for IFNα/β signaling during the innate immune response to acute HSV-1 infection in the cornea are incompletely understood. Using a murine ocular infection model, we hypothesized that the stimulator of IFN genes (STING) mediates resistance to HSV-1 infection at the ocular surface and preserves the structural integrity of this mucosal site. Viral pathogenesis, tissue pathology, and host immune responses during ocular HSV-1 infection were characterized by plaque assay, esthesiometry, pachymetry, immunohistochemistry, flow cytometry, and siRNA transfection in wildtype C57BL/6 (WT), STING-deficient (STING−/−), and IFNα/β receptor-deficient (CD118−/−) mice at days 3–5 post infection. The presence of STING was critical for sustained control of HSV-1 replication in the corneal epithelium and neuroinvasion, but loss of STING had a negligible impact with respect to gross tissue pathology. Auxiliary STING-independent IFNα/β signaling pathways were responsible for maintenance of the corneal integrity. Lymphatic vessels, mast cells, and sensory innervation were compromised in CD118−/− mice concurrent with increased tissue edema. STING-dependent signaling led to the upregulation of tetherin, a viral restriction factor we identify is important in containing the spread of HSV-1 in vivo. PMID:26627457
Hegarty, Deborah M; Hermes, Sam M; Largent-Milnes, Tally M; Aicher, Sue A
We examined the substrates for ocular nociception in adult male Sprague-Dawley rats. Capsaicin application to the ocular surface in awake rats evoked nocifensive responses and suppressed spontaneous grooming responses. Thus, peripheral capsaicin was able to activate the central pathways encoding ocular nociception. Our capsaicin stimulus evoked c-Fos expression in a select population of neurons within rostral trigeminal nucleus caudalis in anesthetized rats. These activated neurons also received direct contacts from corneal afferent fibers traced with cholera toxin B from the corneal surface. However, the central terminals of the corneal afferents that contacted capsaicin-activated trigeminal neurons did not contain TRPV1. To determine if TRPV1 expression had been altered by capsaicin stimulation, we examined TRPV1 content of corneal afferents in animals that did not receive capsaicin stimulation. These studies confirmed that while TRPV1 was present in 30% of CTb-labeled corneal afferent neurons within the trigeminal ganglion, TRPV1 was only detected in 2% of the central terminals of these corneal afferents within the trigeminal nucleus caudalis. Other TRP channels were also present in low proportions of central corneal afferent terminals in unstimulated animals (TRPM8, 2%; TRPA1, 10%). These findings indicate that a pathway from the cornea to rostral trigeminal nucleus caudalis is involved in corneal nociceptive transmission, but that central TRP channel expression is unrelated to the type of stimulus transduced by the peripheral nociceptive endings. Copyright © 2014 Elsevier B.V. All rights reserved.
Hegarty, Deborah M.; Hermes, Sam M.; Largent-Milnes, Tally M.; Aicher, Sue A.
We examined the substrates for ocular nociception in adult male Sprague-Dawley rats. Capsaicin application to the ocular surface in awake rats evoked nocifensive responses and suppressed spontaneous grooming responses. Thus, peripheral capsaicin was able to activate the central pathways encoding ocular nociception. Our capsaicin stimulus evoked c-Fos expression in a select population of neurons within rostral trigeminal nucleus caudalis in anesthetized rats. These activated neurons also received direct contacts from corneal afferent fibers traced with cholera toxin B from the corneal surface. However, the central terminals of the corneal afferents that contacted capsaicin-activated trigeminal neurons did not contain TRPV1. To determine if TRPV1 expression had been altered by capsaicin stimulation, we examined TRPV1 content of corneal afferents in animals that did not receive capsaicin stimulation. These studies confirmed that while TRPV1 was present in 30% of CTb-labeled corneal afferent neurons within the trigeminal ganglion, TRPV1 was only detected in 2% of the central terminals of these corneal afferents within the trigeminal nucleus caudalis. Other TRP channels were also present in low proportions of central corneal afferent terminals in unstimulated animals (TRPM8, 2%; TRPA1, 10%). These findings indicate that a pathway from the cornea to rostral trigeminal nucleus caudalis is involved in corneal nociceptive transmission, but that central TRP channel expression is unrelated to the type of stimulus transduced by the peripheral nociceptive endings. PMID:24996127
Yin, Ji-Qing; Liu, Wen-Qiang; Liu, Chao; Zhang, Yi-Hua; Hua, Jin-Lian; Liu, Wei-Shuai; Dou, Zhong-Ying; Lei, An-Min
Limbal epithelial stem cells are responsible for the self-renewal and replenishment of the corneal epithelium. Although it is possible to repair the ocular surface using limbal stem cell transplantation, the mechanisms behind this therapy are unclear. To investigate the distribution of surviving donor cells in a reconstructed corneal epithelium, we screened a Venus-labeled limbal stem cell strain in goats. Cells were cultivated on denuded human amniotic membrane for 21 days to produce Venus-labeled corneal epithelial sheets. The Venus-labeled corneal epithelial sheets were transplanted to goat models of limbal stem cell deficiency. At 3 months post-surgery, the damaged corneal epithelia were obviously improved in the transplanted group compared with the non-transplanted control, with the donor cells still residing in the reconstructed ocular surface epithelium. Using Venus as a marker, our results indicated that the location and survival of donor cells varied, depending on the corneal epithelial region. Additionally, immunofluorescent staining of the reconstructed corneal epithelium demonstrated that many P63(+) cells were unevenly distributed among basal and suprabasal epithelial layers. Our study provides a new model, and reveals some of the mechanisms involved in corneal epithelial cell regeneration research.
Zhang, Bin; Ma, Jing-Xue; Liu, Dan-Yan; Guo, Cong-Rong; Du, Ying-Hua; Guo, Xiu-Jin; Cui, Yue-Xian
AIM To evaluate the effects of posterior corneal surface measurements on the accuracy of total estimated corneal astigmatism. METHODS Fifty-seven patients with toric intraocular lens (IOL) implantation and posterior corneal astigmatism exceeding 0.5 diopter were enrolled in this retrospective study. The keratometric astigmatism (KA) and total corneal astigmatism (TA) were measured using a Pentacam rotating Scheimpflug camera to assess the outcomes of AcrySof IOL implantation. Toric IOLs were evaluated in 26 eyes using KA measurements and in 31 eyes using TA measurements. Preoperative corneal astigmatism and postoperative refractive astigmatism were recorded for statistical analysis. The cylindrical power of toric IOLs was estimated in all eyes. RESULTS In all cases, the difference of toric IOL astigmatism magnitude between KA and TA measurements for the estimation of preoperative corneal astigmatism was statistically significant. Of a total of 57 cases, the 50.88% decreased from Tn to Tn-1, and 10.53% decreased from Tn to Tn-2. In all cases, 5.26% increased from Tn to Tn+1. The mean postoperative astigmatism within the TA group was significantly lower than that in the KA group. CONCLUSION The accuracy of total corneal astigmatism calculations and the efficacy of toric IOL correction can be enhanced by measuring both the anterior and posterior corneal surfaces using a Pentacam rotating Scheimpflug camera. PMID:27672591
Oztas, Zafer; Barut Selver, Ozlem; Akkin, Cezmi; Canturk, Ecem; Afrashi, Filiz
In our study, we aimed to investigate the correlation of handheld infrared skin thermometer and videothermography device for the measurement of corneal temperature. Forty healthy individuals (80 eyes) were enrolled to the study. Participants underwent a detailed ophthalmologic examination and medical history review for excluding any ocular and systemic diseases. The measurements of the central corneal temperature were performed in a room having constant temperature, humidity, and brightness levels. To avoid any variability, all the temperature measurements were performed in the same examination room by a single examiner. The temperature was measured with a handheld infrared skin thermometer (MEDISANA, FTN) from the corneal surface. The same instrument was also used to measure the subjects' body temperature. Moreover, the subjects underwent the corneal temperature measurement by a noncontact videothermography device (Optris PI 450; Optris GmbH). The male to female ratio was 19:21 among the subjects. The mean age was 25.1±4.7 years. The mean body temperature was 36.93±0.33°C. The mean corneal temperatures measured by the handheld infrared skin thermometer and the ocular videothermography device were 36.94±0.28°C and 35.61±0.61°C, respectively (P<0.01). The mean temperature difference was 1.34±0.57°C, with a 95% confidence interval. There was a moderate correlation between the corneal temperatures measured by the 2 devices in the right, the left eyes, and both eyes, respectively (P=0.450, 0.539, 0.490). Handheld infrared skin thermometers can be used for the evaluation of the corneal temperature. These devices may provide a simple, practical, and cheaper way to detect the corneal temperature, and the widely performed corneal temperature measurements may afford us to understand the temperature variability in numerous ocular conditions in a better way.
Sinnott, Loraine T.
Purpose. The purpose of this study was to examine ocular surface and tear film, contact lens, care solution, medical, and patient-related factors that are associated with corneal staining in contact lens wearers. Methods. In this cross-sectional/nested case–control study, in addition to the assessment of corneal staining with fluorescein, a variety of tear film and ocular surface, contact lens, and patient-related factors were examined. Poisson regression models were used to examine the relation between corneal staining and these factors. Results. Data from 413 patients were eligible for the analyses described. The average age was 30.6 ± 11.1 years, and 277 (67.1%) of the patients were women. Several factors were shown to be related to increased corneal staining in multivariate modeling, including increased daily wearing times (P = 0.0006), lower income (P = 0.0008), lissamine green conjunctival staining (P = 0.002), contact lens deposition (P = 0.007), increased tear meniscus height (P = 0.007), and decreased hydrogel nominal water content (P = 0.02). The wearing of silicone hydrogels (as opposed to hydrogels) was protective against corneal staining (P = 0.0004). Notably, neither contact lens care solutions nor disinfectants were associated with corneal staining. Conclusions. Corneal staining in contact lens wearers continues to be a frequent, but not well understood, outcome. These data suggest that contact lens factors (water content, material, wearing time, and deposition) are more generally associated with corneal staining than are contact lens care solutions or other ocular surface and tear film, demographic, or medical factors. PMID:21087960
Donnenfeld, E D; Schrier, A; Perry, H D; Ingraham, H J; Lasonde, R; Epstein, A; Farber, B
BACKGROUND: Corneal perforation is an uncommon complication associated with keratoconus. The first cases of infectious keratitis and corneal perforation associated with corneal hydrops and contact lens wear are reported in two keratoconus patients. METHODS: A retrospective chart review and histopathological examination were carried out. RESULTS: Both patients progressed to corneal perforation and emergency penetrating keratoplasty. One patient cultured Fusarium and the second patient Serratia marcesens. Both patients wore contact lenses against medical advice. CONCLUSIONS: The tear in Descement's membrane, stromal oedema, and epithelial bedewing associated with corneal hydrops results in loss of the epithelial-endothelial barrier of the cornea, creating a conduit for infectious organisms through the cornea. Acute hydrops associated with epithelial keratitis, stromal swelling, and a Descement's membrane tear may be a significant risk factor for infectious keratitis and corneal perforation. Contact lenses should not be worn during an active corneal hydrops owing to the increased risk for severe infectious keratitis and corneal perforation. Images PMID:8695560
He, Zhiguo; Forest, Fabien; Gain, Philippe; Rageade, Damien; Bernard, Aurélien; Acquart, Sophie; Peoc’h, Michel; Defoe, Dennis M.; Thuret, Gilles
Corneal endothelial cells (CECs) are terminally differentiated cells, specialized in regulating corneal hydration and transparency. They are highly polarized flat cells that separate the cornea from the aqueous humor. Their apical surface, in contact with aqueous humor is hexagonal, whereas their basal surface is irregular. We characterized the structure of human CECs in 3D using confocal microscopy of immunostained whole corneas in which cells and their interrelationships remain intact. Hexagonality of the apical surface was maintained by the interaction between tight junctions and a submembraneous network of actomyosin, braced like a drum. Lateral membranes, which support enzymatic pumps, presented complex expansions resembling interdigitated foot processes at the basal surface. Using computer-aided design and drafting software, we obtained a first simplified 3D model of CECs. By comparing their expression with those in epithelial, stromal and trabecular corneal cells, we selected 9 structural or functional proteins for which 3D patterns were specific to CECs. This first 3D map aids our understanding of the morphologic and functional specificity of CECs and could be used as a reference for characterizing future cell therapy products destined to treat endothelial dysfunctions. PMID:27381832
Tankam, Patrice; He, Zhiguo; Chu, Ying-Ju; Won, Jungeun; Canavesi, Cristina; Lepine, Thierry; Hindman, Holly B; Topham, David J; Gain, Philippe; Thuret, Gilles; Rolland, Jannick P
Gabor-domain optical coherence microscopy (GD-OCM) was applied ex vivo in the investigation of corneal cells and their surrounding microstructures with particular attention to the corneal endothelium. Experiments using fresh pig eyeballs, excised human corneal buttons from patients with Fuchs' endothelial dystrophy (FED), and healthy donor corneas were conducted. Results show in a large field of view (1 mm×1 mm) high definition images of the different cell types and their surrounding microstructures through the full corneal thickness at both the central and peripheral locations of porcine corneas. Particularly, an image of the endothelial cells lining the bottom of the cornea is highlighted. As compared to healthy human corneas, the corneas of individuals with FED show characteristic microstructural alterations of the Descemet's membrane and increased size and number of keratocytes. The GD-OCM-based imaging system developed may constitute a novel tool for corneal imaging and disease diagnosis. Also, importantly, it may provide insights into the mechanism of corneal physiology and pathology, particularly in diseases of the corneal endothelium.
Maloney, R K; Bogan, S J; Waring, G O
Keratometry provides useful information about the cornea's image-forming properties, such as corneal astigmatism, but is inaccurate on irregular corneas. Quantitative corneal topographic information is now obtainable on irregular corneas, but is difficult for the clinician to interpret. We developed a method to determine the spherical power, astigmatism, and topographic irregularity of a cornea by finding the best-fit spherocylinder that was closest to its measured topography. Keratometric measurements and two videokeratographs were gathered prospectively on 262 normal and abnormal corneas. The best-fit measurements of spherical power, astigmatism, and topographic irregularity were reproducible with one standard deviation of 0.75 diopter or better; agreement with keratometric measurements in normal eyes was good (0.60 diopter or better). Topographic irregularity averaged 0.1 diopter on precision spheres, 0.4 diopter on 146 normal eyes, 0.8 diopter on 29 eyes after radial keratotomy, 2.0 diopters on 58 eyes after penetrating keratoplasty, and 3.0 diopters on 29 eyes with advanced keratoconus. We conclude the following: basic corneal image-forming properties can be measured from videokeratographs; the properties can be determined, by our methods, on irregular corneas in which keratometry is unreliable; and topographic irregularity provides a measure of irregular astigmatism.
Armengol-Cruz, Victor de Emanuel; Osorio-Infante, Arturo I.; Campos-García, Manuel; Cossio-Guerrero, Cesar; Díaz-Uribe, José Rufino
In this work, we will present some improvements to the conical null-screen based corneal topographer, for testing aspheric surfaces without rotational symmetry. We present the formulae to design the conical null-screen in such a way that the image on the CCD is a perfect array of spots; departures from this geometry are due to deformation or misalignment of the surface. Additionally, we will explain how to improve the algorithms to find the normals of corneal surface. Finally, we will evaluate the topography of a spherical surface.
Belin, M W; Cambier, J L; Nabors, J R; Ratliff, C D
The PAR Corneal Topography System (CTS) is a computer-driven corneal imaging system which uses close-range photogrammetry (rasterphotogrammetry) to measure and produce a topographic map of the corneal surface. The PAR CTS makes direct point-by-point measurements of surface elevation using a stereo-triangulation technique. The CTS uses a grid pattern composed of horizontal and vertical lines spaced about 0.2 mm (200 microns) apart. Each grid intersection comprises a surface feature which can be located in multiple images and used to generate an (x,y,z) coordinate. Unlike placido disc-based videokeratoscopes, the PAR CTS requires neither a smooth reflective surface nor precise spatial alignment for accurate imaging. In addition to surface elevation, the PAR CTS computes axial and tangential curvatures and refractive power. Difference maps are available in all curvatures, refractive power, and in absolute elevation.
Simirskiĭ, V N
In this review, the features of the regeneration of corneal tissue and its disorders leading to the development of fibrosis are considered. The data on the presence of stem (clonogenic) cell pool in the corneal tissues (epithelium, endothelium, stroma) are given; these cells can serve as a source for regeneration of the tissues at injury or various diseases. The main steps of regeneration of corneal tissues and their disorders that lead to outstripping proliferation of myofibroblasts and secretion of extracellular matrix in the wound area and eventually cause the formation of connective tissue scar and corneal opacity are considered. Particular attention is given to the successes of translational medicine in the treatment of corneal tissue fibrosis. The methods of cell therapy aimed at the restoration of stem cell pool of corneal tissues are the most promising. Gene therapy provides more opportunities; one of its main objectives is the suppression of the myofibroblast proliferation responsible for the development of fibrosis.
Ouchi, M; Kinoshita, S
Purpose To evaluate the postoperative outcomes of cataract eyes complicated with coexisting ocular pathologies that underwent implantation of a refractive multifocal intraocular lens (MIOL) with a surface-embedded near section. Methods LENTIS MPlus (Oculentis GmbH) refractive MIOLs were implanted in 15 eyes with ocular pathologies other than cataract (ie, six high-myopia eyes with an axial length longer than 28 mm, two fundus albipunctatus eyes, two branch retinal-vein occlusion eyes, four glaucoma eyes (one with high myopia), and two keratoconus eyes). Uncorrected or corrected distance and near visual acuity (VA) (UDVA, UNVA, CDVA, and CNVA), contrast sensitivity, and defocus curve were measured at 1 day and 6 months postoperatively, and each patient completed a 6-month postoperative questionnaire regarding vision quality and eyeglass use. Results Thirteen eyes (87%) registered 0 or better in CDVA and 12 eyes (73%) registered better than 0 in CNVA. Contrast sensitivity in the eyes of all patients was comparable to that of normal healthy subjects. No patient required eyeglasses for distance vision, but three patients (20%) required them for near vision. No patient reported poor or very poor vision quality. Conclusion With careful case selection, sectorial refractive MIOL implantation is effective for treating cataract eyes complicated with ocular pathologies. PMID:25744442
Xu, K P; Li, X F; Yu, F S
The main goal of the present study was to investigate the response of cultured bovine corneas to the application of irritant substances and its potential use for predicting ocular irritancy in humans. We hypothesized that chemicals causing eye irritation may induce disruption of epithelial tight junctions and trigger cell stress responses modulated via transcription factors such as AP-1 and NF-kappaB. A simple air-lifted corneal organ culture system was used as an ex vivo model for ocular irritancy test. The effects of two surfactants, sodium dodecyl sulfate (SDS) and benzalkonium chloride (BAK), on corneal epithelial permeability and DNA-binding activity of AP-1 and NF-kappaB were studied in cultured bovine corneas. Both SDS and BAK induced tight junction disruption and increased permeability of corneal epithelium assessed using surface biotinylation in a concentration- and time-dependent manner. An increase in DNA-binding activity measured using electrophoretic mobility shift assay was observed when cultured corneas were treated with surfactants at concentrations causing minimal to mild ocular irritation, indicating epithelial cell stress response. Furthermore, exposure of cultured corneas to SDS or BAK at concentrations causing severe ocular irritancy resulted in a decrease in DNA-binding activity of these transcription factors in epithelial cells. These results indicate that the combination of corneal organ culture and measurements of corneal epithelial permeability and DNA-binding activity of stress-response transcription factors following chemical exposure has the potential to be used as a mechanistically based alternative to in vivo animal testing.
Torricelli, Andre A M; Santhanam, Abirami; Wu, Jiahui; Singh, Vivek; Wilson, Steven E
The corneal wound healing response, including the development of stromal opacity in some eyes, is a process that often leads to scarring that occurs after injury, surgery or infection to the cornea. Immediately after epithelial and stromal injury, a complex sequence of processes contributes to wound repair and regeneration of normal corneal structure and function. In some corneas, however, often depending on the type and extent of injury, the response may also lead to the development of mature vimentin+ α-smooth muscle actin+ desmin+ myofibroblasts. Myofibroblasts are specialized fibroblastic cells generated in the cornea from keratocyte-derived or bone marrow-derived precursor cells. The disorganized extracellular matrix components secreted by myofibroblasts, in addition to decreased expression of corneal crystallins in these cells, are central biological processes that result in corneal stromal fibrosis associated with opacity or "haze". Several factors are associated with myofibroblast generation and haze development after PRK surgery in rabbits, a reproducible model of scarring, including the amount of tissue ablated, which may relate to the extent of keratocyte apoptosis in the early response to injury, irregularity of stromal surface after surgery, and changes in corneal stromal proteoglycans, but normal regeneration of the epithelial basement membrane (EBM) appears to be a critical factor determining whether a cornea heals with relative transparency or vision-limiting stromal opacity. Structural and functional abnormalities of the regenerated EBM facilitate prolonged entry of epithelium-derived growth factors such as transforming growth factor β (TGF-β) and platelet-derived growth factor (PDGF) into the stroma that both drive development of mature myofibroblasts from precursor cells and lead to persistence of the cells in the anterior stroma. A major discovery that has contributed to our understanding of haze development is that keratocytes and corneal
Droy-Lefaix, Marie Thérèse; Bueno, Lionel; Caron, Philippe; Belot, Eric; Roche, Olivier
Purpose. The aim of this study was to evaluate the interest of an ophthalmic eyedrop preparation containing a myosin light chain kinase (MLCK) inhibitor, ML-7, in the treatment of ocular surface. The local protective effect on the inflammation and the increase of corneal permeability induced by benzalkonium (BAK) was evaluated. Methods. An ocular instillation of 10 μL BAK at a concentration of 0.1% in PBS was performed on rats. The eyes were rinsed with sterilized water, 10 minutes after BAK preceded by instillation at T −24, −12, and −0.5 hours of 10 μL of ML-7: 100 μg (10 μL) into a gel form vehicle. All animals were sacrificed 6 hours after BAK instillation. The eyes were isolated for study in a masked manner. The ocular surface inflammation was assessed by measuring the inflammatory cell infiltration by a histologic quantitative analysis and for total ocular myeloperoxidase (MPO) activity. The tight junction permeability was tested. Results. Instillation of 0.1% BAK increased the inflammation of the eye. The quantitative analysis showed an increase in the number of eosinophil and neutrophil polynuclears, and MPO activity. Pretreatment with ML-7 reduced inflammation (P < 0.05). The vehicle alone produced no notable effects. BAK instillation also thickened the fluorescent corneal front on frozen sections, indicating an increase of tight junction permeability. Pretreatment with ML-7 suppressed BAK-induced alterations of paracellular permeability while the vehicle had no visible effects. Conclusions. Our study indicates that the inhibition of corneal cytoskeleton contraction by an MLCK inhibitor prevents BAK-induced ocular inflammatory response, and that ML-7 may be a new and original preparation in the treatment of ocular surface pathologies. PMID:23518768
Bergmanson, J P; Ruben, M; Chu, L W
The comparative corneal epithelial effects of rigid gas permeable and soft contact lenses are reported in the present preliminary study using two bush baby monkeys (Galago senegalensis). Both types of lenses produced early cell death among the surface squamous cells while internally the epithelium and its nerve fibers remained normal. Sporadically small abnormal groups of cells involving two to three of the surface layers were observed in both the hard and soft lens wearing corneas. It was concluded that this represented superficial punctate keratitis (SPK). Small superficial intracellular epithelial cysts with membranous contents were infrequently noted in the gas permeable lens wearing cornea and it is suggested here that they were mild forms or precursors of those seen clinically in human corneas. Since the gas permeable lens met the corneal oxygen requirement it is postulated that the traumatic effect of the rigidity of the lens caused the cystic formation to occur. The relative hypoxia induced by the soft contact lens resulted in a mild superficial epithelial edema.
Al-Mahmood, Ammar M.; Al-Swailem, Samar A.; Edward, Deepak P.
Glaucoma after corneal transplantation is a leading cause of ocular morbidity after penetrating keratoplasty. The incidence reported is highly variable and a number of etiologic factors have been identified. A number of treatment options are available; surgical intervention for IOP control is associated with a high incidence of graft failure. IOP elevation is less frequently seen following deep anterior lamellar keratoplasty. Descemet's striping-automated endothelial keratoplasty is also associated with postprocedure intraocular pressure elevation and secondary glaucoma and presents unique surgical challenges in patients with preexisting glaucoma surgeries. Glaucoma exists in up to three-quarters of patients who undergo keratoprosthesis surgery and the management if often challenging. The aim of this paper is to highlight the incidence, etiology, and management of glaucoma following different corneal transplant procedures. It also focuses on the challenges in the diagnosis of glaucoma and intraocular pressure monitoring in this group of patients. PMID:22315661
Efron, N; Young, G; Brennan, N A
A wide-field color-coded infra-red imaging device was applied to the measurement of i) the temperature profile across the ocular surface and ii) the temporal stability of central corneal temperature, on 21 subjects. The thermographs showed a pattern of ellipsoidal isotherms (major axis horizontal) approximately concentric about a temperature apex (coldest point) which was slightly inferior to the geometric center of the cornea (GCC). The GCC had a mean temperature (+/- SD) of 34.3 +/- 0.7 degrees C (range 32.8 to 35.4 degrees C). Temperature increased towards the periphery of the cornea with the limbus being 0.45 degrees C warmer than the GCC (p less than 0.0001). Following a blink, the GCC cooled at a mean (+/- SD) rate of 0.033 +/- 0.024 degrees C/s (p less than 0.0001) over the first 15s. Subjects whose corneas cooled more slowly following a blink demonstrated a greater capacity to avoid blinking for a prolonged period (p less than 0.05). This improved method of measuring ocular surface temperature has important applications in modeling corneal physiology and pathology.
Steijns, Daan; Bral, Nathalie; Tang, Mei Lie; van der Lelij, Allegonda
Corneal transplants are the most frequently performed human transplant procedure. In the last decade, we have seen large developments in the field of corneal transplant surgery. Currently, several techniques are being used in the Netherlands, each with its own advantages and disadvantages and with distinct indications. In penetrating keratoplasty all layers of the cornea are replaced by a donor cornea. In so-called lamellar corneal transplantation only the affected layer of the cornea is replaced by donor tissue. The developments in corneal transplantation surgery have resulted in an improved prognosis in terms of vision and fewer complications.
Mikkelsen, Lauge Hjorth; Hamoudi, Hassan; Gül, Cigdem Altuntas; Heegaard, Steffen
Purpose: To present a case of corneal toxicity following exposure to milky plant latex from Asclepias tuberosa. Methods: A 70-year-old female presented with blurred vision and pain in her left eye after handling an Ascepias tuberosa. Clinical examination revealed a corneal stromal oedema with small epithelial defects. The corneal endothelium was intact and folds in Descemets membrane were observed. The oedema was treated with chloramphenicol, dexamethasone and scopolamine. Results: The corneal oedema had appeared after corneal exposure to the plant, Asclepias tuberosa, whose latex contains cardenolides that inhibit the Na+/ K+-ATPase in the corneal endothelium. The oedema resolved after 96 hours. After nine months the best corrected visual acuity was 20/20. Conclusion: Corneal toxicity has previously been reported for plants of the Asclepias family. This is a rare case describing severe corneal toxicity caused by exposure to latex from Asclepias tuberosa. Handling of plants of the Asclepias family should be kept as a differential diagnosis in cases of acute corneal toxicity.
Röck, Tobias; Bramkamp, Matthias; Bartz-Schmidt, Karl Ulrich; Röck, Daniel
In the majority of countries, there is a shortage of donor corneas for corneal transplantations. This study investigated the impact of organ transplantation scandals on corneal donation rate at the University Hospital Tübingen. Each deceased patient was considered as a potential corneal donor. An ophthalmic resident handled with stable methods of procedures the corneal donor procurement from 2009 to 2015. The rates of corneal donation were examined and analyzed. Among the 5712 hospital deaths, consent for corneal donation was obtained in 711 cases. The mean annual corneal donation rate was 12.4%. Since 2009, the donation rate per year could be increased with exception of 2013 and 2015. In the end of 2012 and 2014 two huge organ donation scandals were known in Germany. In the following years 2013 and 2015 corneal donation rate decreased significantly (P=0.0181 and P=0.0006). We concluded that transplantation scandals have a significant impact on corneal donation rate. Improving professional's performance through full transparency and honesty is very important to earn trust of potential donors and their families.
Röck, Tobias; Bramkamp, Matthias; Bartz-Schmidt, Karl Ulrich; Röck, Daniel
In the majority of countries, there is a shortage of donor corneas for corneal transplantations. This study investigated the impact of organ transplantation scandals on corneal donation rate at the University Hospital Tübingen. Each deceased patient was considered as a potential corneal donor. An ophthalmic resident handled with stable methods of procedures the corneal donor procurement from 2009 to 2015. The rates of corneal donation were examined and analyzed. Among the 5712 hospital deaths, consent for corneal donation was obtained in 711 cases. The mean annual corneal donation rate was 12.4%. Since 2009, the donation rate per year could be increased with exception of 2013 and 2015. In the end of 2012 and 2014 two huge organ donation scandals were known in Germany. In the following years 2013 and 2015 corneal donation rate decreased significantly (P=0.0181 and P=0.0006). We concluded that transplantation scandals have a significant impact on corneal donation rate. Improving professional's performance through full transparency and honesty is very important to earn trust of potential donors and their families. PMID:28730094
Purpose. To evaluate the changes in epithelial thickness profile following transepithelial photorefractive keratectomy (T-PRK) for myopia and to investigate the effect of epithelial remodeling on corneal asphericity. Methods. Forty-four patients (44 right eyes) who underwent T-PRK were retrospectively evaluated. Epithelial thickness was measured using spectral-domain optical coherence tomography at different corneal zones (central, 2 mm; paracentral, 2–5 mm; and mid-peripheral, 5-6 mm) preoperatively and at 1 week and 1, 3, and 6 months postoperatively. The correlation between the changes in corneal epithelial thickness (ΔCET) and postoperative Q-value changes (ΔQ) was analyzed 6 months postoperatively. Results. Epithelial thickness at 6 months showed a negative meniscus-like lenticular pattern with less central thickening, which increased progressively toward the mid-periphery (3.69 ± 4.2, 5.19 ± 3.8, and 6.23 ± 3.9 μm at the center, paracenter, and mid-periphery, resp., P < 0.01). A significant positive relationship was observed between epithelial thickening and ΔQ 6 months postoperatively (r = 0.438, 0.580, and 0.504, resp., P < 0.01). Conclusions. Significant epithelial thickening was observed after T-PRK and showed a lenticular change with more thickening mid-peripherally, resulting in increased oblateness postoperatively. Epithelial remodeling may modify the epithelial thickness profile after surface ablation refractive surgery for myopia. PMID:27672447
Navarro Martínez-Cantullera, A; Calatayud Pinuaga, M
Cornea transplant is the most common tissue transplant in the world. In Spain, tissue donation activities depend upon transplant coordinator activities and the well-known Spanish model for organ and tissue donation. Tissue donor detection system and tissue donor evaluation is performed mainly by transplant coordinators using the Spanish model on donation. The evaluation of a potential tissue donor from detection until recovery is based on an exhaustive review of the medical and social history, physical examination, family interview to determine will of the deceased, and a laboratory screening test. Corneal acceptance criteria for transplantation have a wider spectrum than other tissues, as donors with active malignancies and infections are accepted for kearatoplasty in most tissue banks. Corneal evaluation during the whole process is performed to ensure the safety of the donor and the recipient, as well as an effective transplant. Last step before processing, corneal recovery, must be performed under standard operating procedures and in a correct environment. Copyright © 2016 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.
Objective To report the central corneal thickness (CCT) in healthy white, African-American, and Hispanic children from birth to 17 years of age. Design Prospective observational multicenter study. Central corneal thickness was measured with a hand-held contact pachymeter. Results Two thousand seventy-nine children were included in the study, with ages ranging from day of birth to 17 years. Included were 807 white, 494 Hispanic, and 474 African-American individuals, in addition to Asian, unknown and mixed race individuals. African-American children had thinner corneas on average than that of both white (p< .001) and Hispanic children (p< .001) by approximately 20 micrometers. Thicker median CCT was observed with each successive year of age from age 1 to 11 years, with year-to-year differences steadily decreasing and reaching a plateau after age 11 at 573 micrometers in white and Hispanic children and 551 micrometers in African-American children. For every 100 micrometers of thicker CCT measured, the intraocular pressure was 1.5 mmHg higher on average (p< 0.001). For every diopter of increased myopic refractive error (p< 0.001) CCT was 1 micrometer thinner on average. Conclusions Median CCT increases with age from 1 to 11 years with the greatest increase present in the youngest age groups. African-American children on average have thinner central corneas than white and Hispanic children, while white and Hispanic children demonstrate similar central corneal thickness. PMID:21911662
Kamiya, Kazutaka; Shimizu, Kimiya; Igarashi, Akihito; Miyake, Toshiyuki
To investigate the magnitudes and the axis orientations of anterior, posterior, and total central corneal astigmatism in eyes with keratoconus. Retrospective case series. This study comprised 137 eyes of 137 keratoconic patients (97 men and 40 women; mean age ± standard deviation, 36.9 ± 12.2 years). The magnitude and the axis orientation of each corneal astigmatism were determined with a rotating Scheimpflug system. The mean magnitudes of anterior, posterior, and total central corneal astigmatism were 3.93 ± 2.74 diopters (D), 0.93 ± 0.64 D, and 3.90 ± 2.75 D, respectively. With-the-rule (WTR), against-the-rule (ATR), and oblique astigmatism of the anterior corneal surface was found in 90 eyes (65.7%), 33 eyes (24.1%), and 14 eyes (10.2%), respectively, whereas the corresponding astigmatism of the posterior corneal surface was found in 14 eyes (10.2%), 15 eyes (10.9%), and 108 eyes (78.8%), respectively. We found a significant correlation between the magnitudes of anterior and posterior corneal astigmatism (Pearson correlation coefficient r = 0.769, P < .001). The mean magnitudes of anterior and posterior corneal astigmatism were approximately 4 D and 1 D, respectively, in eyes with keratoconus. Approximately 65% and 80% of eyes showed that WTR anterior astigmatism and ATR posterior astigmatism, respectively. The presence of posterior corneal astigmatism is not necessarily negligible for the accurate astigmatic correction of toric intraocular lens implantation or rigid gas-permeable contact lens wear for keratoconus. Copyright © 2015 Elsevier Inc. All rights reserved.
Graue-Hernandez, Enrique O; Zuñiga-Gonzalez, Isaac; Hernandez-Camarena, Julio C; Jaimes, Martha; Chirinos-Saldaña, Patricia; Navas, Alejandro; Ramirez-Miranda, Arturo
Purpose. To report a case of severe corneal thinning secondary to dry eye treated with a tectonic Descemet stripping automated lamellar keratoplasty (DSAEK) and amniotic membrane graft. Methods. A 72-year-old man with a history of long standing diabetes mellitus type 2 and dry eye presented with 80% corneal thinning and edema on the right eye and no signs of infectious disease, initially managed with topical unpreserved lubrication and 20% autologous serum drops. Eight weeks after, the defect advanced in size and depth until Descemetocele was formed. Thereafter, he underwent DSAEK for tectonic purposes. One month after the procedure, the posterior lamellar graft was well adhered but a 4 mm epithelial defect was still present. A multilayered amniotic membrane graft was then performed. Results. Ocular surface healed quickly and reepithelization occurred over a 2-week period. Eight months after, the ocular surface remained stable and structurally adequate. Conclusion. Tectonic DSAEK in conjunction with multilayered amniotic graft may not only provide structural support and avoid corneal perforation, but may also promote reepithelization and ocular surface healing and decrease concomitant inflammation.
Graue-Hernandez, Enrique O.; Zuñiga-Gonzalez, Isaac; Hernandez-Camarena, Julio C.; Jaimes, Martha; Chirinos-Saldaña, Patricia; Navas, Alejandro; Ramirez-Miranda, Arturo
Purpose. To report a case of severe corneal thinning secondary to dry eye treated with a tectonic Descemet stripping automated lamellar keratoplasty (DSAEK) and amniotic membrane graft. Methods. A 72-year-old man with a history of long standing diabetes mellitus type 2 and dry eye presented with 80% corneal thinning and edema on the right eye and no signs of infectious disease, initially managed with topical unpreserved lubrication and 20% autologous serum drops. Eight weeks after, the defect advanced in size and depth until Descemetocele was formed. Thereafter, he underwent DSAEK for tectonic purposes. One month after the procedure, the posterior lamellar graft was well adhered but a 4 mm epithelial defect was still present. A multilayered amniotic membrane graft was then performed. Results. Ocular surface healed quickly and reepithelization occurred over a 2-week period. Eight months after, the ocular surface remained stable and structurally adequate. Conclusion. Tectonic DSAEK in conjunction with multilayered amniotic graft may not only provide structural support and avoid corneal perforation, but may also promote reepithelization and ocular surface healing and decrease concomitant inflammation. PMID:23259100
Bhalekar, Swapnil; Sangwan, Virender S; Basu, Sayan
An 11-year-old boy underwent simple limbal epithelial transplantation (SLET) from the healthy right eye to his left eye for total limbal stem cell deficiency. One month later, corneal surface epithelialised and whitish plaques overlying the transplants were seen inferiorly. Those plaques were adherent to the surface of the contact lens and underlying corneal surface had smooth elevations. Similar findings were noted in a 23-year man following cyanoacrylate glue application for corneal perforation. On histological and immunohistochemical analysis, cells lining the contact lenses were identified as corneal epithelial cells. These cases illustrate epithelial cell growth on the contact lens and epithelial hyperplasia on corresponding surface of the cornea. Exorbitant proliferation of the epithelial cells may be owing to young age; therefore, early contact lens removal after SLET in young age, can possibly avoid epithelial hyperplasia. This also reiterates the possibility of using contact lens as a scaffold to grow epithelial cells.
Safaeian, Reza; Hassani, Valiollah; Faiz, Hamid Reza
BACKGROUND Diaphragmatic rupture can be seen in up to 5% of car accidents, and 80%-100% of diaphragmatic hernias are associated with other vital organ injuries. Brain, pelvis, long bones, liver, spleen, and aorta are some other organs that can be severely damaged and need different anesthetic managements. CASE REPORT A 37-year-old male victim of a head-on collision who was suffering diaphragmatic rupture and corneal laceration was prepared for an emergency operation 11 hours after the car accident. Gastric decompression, pre-oxygenation, rapid sequence induction with succinylcholine, immediate use of non-depolarizing muscle relaxant, and mechanical ventilation with low tidal volume after intubation were used in anesthetic management of the patient. CONCLUSIONS Because of the high prevalence of coexisting pathologies with traumatic diaphragmatic hernia, anesthetic management must be tailored to the associated pathologies.
Parissi, Marlen; Randjelovic, Stefan; Poletti, Enea; Guimarães, Pedro; Ruggeri, Alfredo; Fragkiskou, Sofia; Wihlmark, Thu Ba; Utheim, Tor Paaske; Lagali, Neil
It is unknown whether a neurotrophic deficit or pathologic nerve morphology persists in keratoconus in the long term after corneal collagen cross-linking (CXL) treatment. Nerve pathology could impact long-term corneal status in patients with keratoconus. To determine whether CXL treatment of keratoconus results in normalization of subbasal nerve density and architecture up to 5 years after treatment. Observational study of 19 patients with early-stage keratoconus indicated for a first CXL treatment with longitudinal follow-up to 5 years postoperatively (examinations were performed from 2009 to 2015; analysis was performed from February to May 2015) and 19 age-matched healthy volunteers at a primary care center and a university hospital ophthalmology department. The patients with keratoconus underwent standard epithelial-off UV-A/riboflavin CXL treatment with 30-minute UV-A exposure at 3 mW/cm2 irradiance. Central corneal subbasal nerve density and subbasal nerve architecture by use of laser-scanning in vivo confocal microscopy; subbasal nerve analysis by 2 masked observers and by use of a fully automated method; wide-field mosaics of subbasal nerve architecture by use of an automated method; and ocular surface touch sensitivity by use of contact esthesiometry. Mean (SD) age of the 19 patients with keratoconus was 27.5 (7.1) years (range, 19-44 years), and minimal corneal thickness was 428 (36) μm (range, 372-497 μm). Compared with the mean (SD) preoperative subbasal nerve density of 21.0 (4.2) mm/mm2 in healthy corneas, the mean (SD) preoperative subbasal nerve density of 10.3 (5.6) mm/mm2 in the corneas of patients with stage 1 or 2 keratoconus was reduced 51% (mean difference, 10.7 mm/mm2 [95% CI, 6.8-14.6 mm/mm2]; P < .001). After CXL, nerves continued to regenerate for up to 5 years, but nerve density remained reduced relative to healthy corneas at final follow-up (mean reduction, 8.5 mm/mm2 [95% CI, 4.7-12.4 mm/mm2]; P < .001) despite recovery of touch
Han, Zhaolong; Li, Jiasong; Singh, Manmohan; Wu, Chen; Liu, Chih-Hao; Raghunathan, Raksha; Aglyamov, Salavat R; Vantipalli, Srilatha; Twa, Michael D; Larin, Kirill V
The biomechanical properties of the cornea play a critical role in forming vision. Diseases such as keratoconus can structurally degenerate the cornea causing a pathological loss in visual acuity. UV-A/riboflavin corneal collagen crosslinking (CXL) is a clinically available treatment to stiffen the cornea and restore its healthy shape and function. However, current CXL techniques do not account for pre-existing biomechanical properties of the cornea nor the effects of the CXL treatment itself. In addition to the inherent corneal structure, the intraocular pressure (IOP) can also dramatically affect the measured biomechanical properties of the cornea. In this work, we present the details and development of a modified Rayleigh-Lamb frequency equation model for quantifying corneal biomechanical properties. After comparison with finite element modeling, the model was utilized to quantify the viscoelasticity of in situ porcine corneas in the whole eye-globe configuration before and after CXL based on noncontact optical coherence elastography measurements. Moreover, the viscoelasticity of the untreated and CXL-treated eyes was quantified at various IOPs. The results showed that the stiffness of the cornea increased after CXL and that corneal stiffness is close to linear as a function of IOP. These results show that the modified Rayleigh-Lamb wave model can provide an accurate assessment of corneal viscoelasticity, which could be used for customized CXL therapies.
Krysik, Katarzyna; Lyssek-Boron, Anita; Jankowska-Szmul, Judyta; Wylegala, Edward A.
Purpose. To report the surgical approach, anatomical and functional results, and complications in the group of patients with corneal perforation. Materials and Methods. 247 eyes with corneal perforation were operated on between January 2010 and July 2016. The three surgical procedures, dependent on size and location of perforation, were performed: full-sized penetrating keratoplasty, corneoscleral patch graft, and anterior lamellar keratoplasty. The eyes underwent the minimum 6-month follow-up visit. Results. Between January 2010 and July 2016, 247 surgeries were performed: 116 penetrating keratoplasties, 117 corneoscleral patch grafts, and 14 anterior lamellar keratoplasties. More than one procedure was necessary in 32 eyes. Final improvement of the visual acuity, within a gain of 2 or more lines with the Snellen test, was achieved in 56 operated eyes. To achieve better final visual acuity, 75 eyes required successive surgical treatment. Complications of the surgery comprised persistent epithelial defect, glaucoma or ocular hypertension, corneal oedema, graft melting, loose corneal sutures, reinfection, anterior synechiae and fibrinoid membranes, and endophthalmitis. In 26 eyes, the treatment failure was reported. Conclusions. There is no one general-purpose surgical technique to treat corneal perforations. The complex nature of this pathology remains the individual, careful but also very distinct and multifactorial approach. PMID:28326192
Bron, Romke; Wood, Rhiannon J; Brock, James A; Ivanusic, Jason J
Recently, a novel class of mechanically sensitive channels has been identified and have been called Piezo channels. In this study, we explored Piezo channel expression in sensory neurons supplying the guinea pig corneal epithelium, which have well-defined modalities in this species. We hypothesized that a proportion of corneal afferent neurons express Piezo2, and that these neurons are neurochemically distinct from corneal polymodal nociceptors or cold-sensing neurons. We used a combination of retrograde tracing to identify corneal afferent neurons and double label in situ hybridization and/or immunohistochemistry to determine their molecular and/or neurochemical profile. We found that Piezo2 expression occurs in ∼26% of trigeminal ganglion neurons and 30% of corneal afferent neurons. Piezo2 corneal afferent neurons are almost exclusively non-calcitonin gene-related peptide (CGRP)-immunoreactive (-IR), medium- to large-sized neurons that are NF200-IR, suggesting they are not corneal polymodal nociceptors. There was no coexpression of Piezo2 and transient receptor potential cation channel subfamily M member 8 (TRPM8) transcripts in any corneal afferent neurons, further suggesting that Piezo2 is not expressed in corneal cold-sensing neurons. We also noted that TRPM8-IR or CGRP-IR corneal afferent neurons are almost entirely small and lack NF200-IR. Piezo2 expression occurs in a neurochemically distinct subpopulation of corneal afferent neurons that are not polymodal nociceptors or cold-sensing neurons, and is likely confined to a subpopulation of pure mechano-nociceptors in the cornea. This provides the first evidence in an in vivo system that Piezo2 is a strong candidate for a channel that transduces noxious mechanical stimuli. © 2014 Wiley Periodicals, Inc.
Rowsey, J. James
An eye with a cornea repaired without sutures comprising a donor material in the shape of a partial sphere having a generally central extent, the central extent being of the size and shape of the central portion of a cornea of an eye, the central extent having a periphery of a fixed diameter with an exterior surface in a convex configuration and an interior surface in a concave configuration and with an essentially common thickness throughout, the central extent having a plurality of corneal flaps extending radially from the periphery of the central extent, the flaps having exterior surfaces as a continuation of the exterior surface of the central extent; and a recipient eye in the shape of a partial sphere having a circular aperture in the cornea at its central portion, the central aperture being of a size and shape essentially that of the periphery of the central extent of the donor material, the aperture being of a common thickness at the periphery of the aperture, the central portion having pockets and with the central extent of the donor material located within the aperture of the recipient eye and with the flaps of the central extent being imbricated into the pockets of the recipient eye.
Niemiec, Brook A
Oral disease is exceedingly common in small animal patients. In addition, there is a very wide variety of pathologies that are encountered within the oral cavity. These conditions often cause significant pain and/or localized and systemic infection; however, the majority of these conditions have little to no obvious clinical signs. Therefore, diagnosis is not typically made until late in the disease course. Knowledge of these diseases will better equip the practitioner to effectively treat them. This article covers the more common forms of oral pathology in the dog and cat, excluding periodontal disease, which is covered in its own chapter. The various pathologies are presented in graphic form, and the etiology, clinical signs, recommended diagnostic tests, and treatment options are discussed. Pathologies that are covered include: persistent deciduous teeth, fractured teeth, intrinsically stained teeth, feline tooth resorption, caries, oral neoplasia, eosinophilic granuloma complex, lymphoplasmacytic gingivostomatitis, enamel hypoplasia, and "missing" teeth.
Wagner, Frank; Meyer-Lindenberg, Andrea; Heider, Hans-Josef; Görig, Christiane; Nolte, Ingo
In order to establish reference values for corneal sensitivity in ophthalmologically healthy persians (n = 40) and domestic short hair cats (n = 60) a prospective study was conducted. Furthermore corneal sensitivity in 48 cats with a corneal sequestrum was measured. Corneal sensitivity was recorded with the help of the aesthesiometer according to Cochet and Bonnet in five different corneal locations (central, nasal, dorsal, temporal, and ventral). The sensitivity for the central corneal region was recorded as amounting to 3.58 +/- 0.56 cm in ophthalmologically healthy domestic short hair cats and to 2.97 +/- 0.58 cm in healthy persian cats. The sensitivity of the central corneal area of a cat with a corneal sequester only amounts to 2.03 +/- 0.53 cm. Between the diseased and the healthy eyes no statistical difference could be demonstrated for any of the measured corneal locations. The sensitivity of the peripheral corneal locations is significantly lower than that of the central corneal region in all three groups examined.
Brinkman, C J; Treffers, W F; Broekhuyse, R M
Patients suffering from various corneal diseases and waiting for keratoplasty have been immunologically investigated in order to establish sensitisation to corneal antigens. The presence of lymphocytes sensitised to the soluble from human corneas, bovine corneal epithelium, and bovine corneal stroma, which all possess common antigenicity, could be demonstrated in 30%, 50%, and 23%, respectively, of all patients. In none of these patients could a positive plasma antibody titre to human corneal antigens be detected. The results suggest the dominance of T-lymphocyte activity. No correlation was found between the degree of corneal vascularisation and the presence of sensitised lymphocytes to human corneal antigens. Arrangement of the patients according to diagnosis showed that especially those suffering from herpes simplex virus keratitis reacted positively to human corneal antigens. A possible explanation is given. Lymphocytes of controls showed no or only very low stimulation with the soluble fractions of human corneas or bovine corneal str