Pathologically Reduced Subbasal Nerve Density in Epithelial Basement Membrane Dystrophy Is Unaltered by Phototherapeutic Keratectomy Treatment

Citation: Germundsson J, Lagali N. Pathologically reduced subbasal nerve density in epithelial basement membrane dystrophy is unaltered by phototherapeutic keratectomy treatment. Invest Ophthalmol Vis Sci. 2014;55:183555: -184155: . DOI:10.1167 PURPOSE. To investigate the effect of phototherapeutic keratectomy (PTK) treatment on corneal epithelial wing cell and corneal subbasal nerve density in epithelial basement membrane dystrophy (EBMD). METHODS. A total of 39 patients with EBMD who underwent PTK treatment, 40 healthy volunteers, and 24 untreated eyes with EBMD were examined with laser-scanning in vivo confocal microscopy (IVCM). Corneal subbasal nerves and epithelial wing cells were manually quantified from IVCM images by two observers, while epithelial wing cells were additionally quantified by a fully automated method. RESULTS. Subbasal nerve density was significantly reduced in untreated (10,164 6 4139 lm/ mm 2 ; n ¼ 24) and PTK-treated (10,624 6 4479 lm/mm 2 ; n ¼ 39) EBMD eyes, relative to healthy controls (18,241 6 4479 lm/mm 2 ; n ¼ 40) (P < 0.001). Subbasal nerve density in PTK-treated and untreated eyes did not differ (P > 0.05). Epithelial wing cell density did not differ between PTK-treated and untreated EBMD eyes, by either manual or automated analysis; however, epithelial wing cell density in PTK-treated EBMD corneas was significantly reduced (P ¼ 0.008) relative to healthy corneas, by automated cell counting. CONCLUSIONS. Subbasal nerve density in EBMD is reduced by 45% and recovers only to the reduced level in the long term after PTK treatment, whereas epithelial wing cell density in EBMD is not affected by PTK in the long term. Fully automated cell analysis from IVCM images could provide an objective, standardized means to quantify and compare corneal cell densities in future studies

Surgical outcomes of phototherapeutic keratectomy on Epithelial basement membrane dystrophy, and the characterisation of Bowman´s Layer

Background. Epithelial basement membrane dystrophy (EBMD) is a common disease of the anterior cornea that can lead to problems with vision and/or painful recurrent erosions of the corneal epithelium. Several treatment options have been used, but recurrence of EBMD after treatment is a problem. Excimer laser phototherapeutic keratectomy (PTK) has become an increasingly popular surgical option in recent years due to its accuracy, reproducibility, and good clinical outcomes. When treating EBMD with PTK, the anterior corneal structures including the epithelium, Bowman´s layer (BL), and subbasal nerves are disrupted or removed completely. Little is known about how BL, nerves, and the stroma recover after PTK treatment, or how they could influence recurrence of EBMD symptoms. Additionally, very little is known about the properties and actual thickness of BL in-vivo. Aims. To improve the understanding and management of EBMD by investigating the clinical diagnosis and treatment of EBMD and its relationship to Bowman´s layer. Method. An excimer laser was used to treat EBMD patients at the Department of Ophthalmology during the period 2001-2010. IVCM was used to perform pre- and postoperative examinations. In particular, images of anterior corneal structures, cells, and nerves in high-resolution were obtained. Additionally, a group of over 100 healthy volunteers underwent a full ophthalmic examination including IVCM. Other subjects examined in this work included a group of 17 patients who underwent full-thickness transplantation of the cornea. Results and conclusions. Clinical follow-up revealed that PTK is an effective method of alleviating the clinical symptoms of EBMD, but the dystrophy can recur with time. Recurrence can be divided into clinical and morphologic types, and may depend upon treatment parameters including the type and depth of ablation. IVCM was found to be a useful screening tool pre- and postoperatively, and could prevent patients with symptoms, but no visible signs of EBMD on slit lamp examination, to go undiagnosed and untreated. BL was found to play a role in regenerative wound healing after PTK, and was also found to be important regarding the treatment and recurrence of EBMD. BL may present a physical barrier that protects the subepithelial nerve plexus thereby facilitating sensory recovery, and BL may also serve as a barrier that prevents direct traumatic contact with the corneal stroma, avoiding a stromal wound healing response. To aid in accurate assessment of BL in patients, an in vivo method for determining BL thickness was developed. This method could be an important tool to aid in clinical assessment and planned treatments of the anterior cornea. Using this tool, a large inter-individual variability in BL thickness and a strong negative correlation of BL thickness with age were found in a healthy population. Using IVCM, it was also found that subbasal nerves are pathologically reduced in EBMD compared to a healthy population, and that this nerve deficit does not improve in the long term after PTK treatment

1D Simulation of Hydraulic Cam Phaser System Utilized in Heavy Duty Vehicles : An Investigation on Attenuation of Phase Oscillations from Cam Torque Disturbances

Cam phasers allow improvements to the efficiency and emissions of internal combustion engines. The usage of hydraulic vane type cam phasers for heavy-duty applications have shown problems with oscillations during testing at \gls{Scania CV}. To investigate the root cause of the oscillations a detailed 1-d simulation model has been created. The 1-d simulation model was calibrated and compared against measurements of a cam phaser system mounted on a physical engine. The 1-d simulation model of the cam phaser system was shown to be able to reproduce the oscillatory behavior seen in engine tests. But there are some concerns regarding the model's reliability, due to its dependence on the integration time step. It was determined that free air in the phaser chambers is causing the excessive oscillations. The source of the free air present in physical phasers are not yet fully understood, but the movement of the phaser control valve, opening and closing of the phaser chamber vents, in conjunction with motion of the phase oscillations has a significant effect on the phaser's chamber pressure, resulting in reduce pressures. The reduced pressures result in air being sucked in to the phaser, form both the oil control valve vent and external chamber leakages. Another potential sources of free air is dissolved air in the oil supply being released due to low pressures from oil pressure fluctuations. A potential solution to increase the stability of the phaser is to reduce the sources of air, by having an oil accumulator at the vent, limiting leakage, having a high and steady oil supply pressure, modifying the oil control valve ports to have a more gradual initial opening area and controlling the oil control valve appropriately. How to implement these implementations and evaluate them are left as future work. Potential improvements to get rid of the 1-d simulation model's dependence on the time step, increasing the model's reliability, are discussed, but not tested

1D Simulation of Hydraulic Cam Phaser System Utilized in Heavy Duty Vehicles : An Investigation on Attenuation of Phase Oscillations from Cam Torque Disturbances

Cam phasers allow improvements to the efficiency and emissions of internal combustion engines. The usage of hydraulic vane type cam phasers for heavy-duty applications have shown problems with oscillations during testing at \gls{Scania CV}. To investigate the root cause of the oscillations a detailed 1-d simulation model has been created. The 1-d simulation model was calibrated and compared against measurements of a cam phaser system mounted on a physical engine. The 1-d simulation model of the cam phaser system was shown to be able to reproduce the oscillatory behavior seen in engine tests. But there are some concerns regarding the model's reliability, due to its dependence on the integration time step. It was determined that free air in the phaser chambers is causing the excessive oscillations. The source of the free air present in physical phasers are not yet fully understood, but the movement of the phaser control valve, opening and closing of the phaser chamber vents, in conjunction with motion of the phase oscillations has a significant effect on the phaser's chamber pressure, resulting in reduce pressures. The reduced pressures result in air being sucked in to the phaser, form both the oil control valve vent and external chamber leakages. Another potential sources of free air is dissolved air in the oil supply being released due to low pressures from oil pressure fluctuations. A potential solution to increase the stability of the phaser is to reduce the sources of air, by having an oil accumulator at the vent, limiting leakage, having a high and steady oil supply pressure, modifying the oil control valve ports to have a more gradual initial opening area and controlling the oil control valve appropriately. How to implement these implementations and evaluate them are left as future work. Potential improvements to get rid of the 1-d simulation model's dependence on the time step, increasing the model's reliability, are discussed, but not tested

Dynamic Verification of a Large Discrete System

Symbolic algebraic analysis techniques are applied to the landing gear subsystem in the new Swedish fighter aircraft, JAS 39 Gripen. Our methods are based on polynomials over finite fields (with Boolean algebra and propositional logic as special cases). Polynomials are used to represent the basic dynamic equations for the processes (controller and plant) as well as static properties of these. Temporal algebra (or temporal logic) is used to represent specifications of system behavior. These specifications are verified both on a model of the landing gear controller, and a model of the closed loop behavior of the landing gear controller connected to a plant. The model of the landing gear controller is made from the actual implementation in Pascal. The tools used are developed by the authors in Mathematica and uses an efficient implementation of binary decision diagrams (BDDs). 1 Introduction We have modeled and analyzed an existing discrete subsystem of a modern fighter aircraft, the lan..

Symbolic Algebraic Discrete Systems - Applied to the JAS 39 Fighter Aircraft

In this document we present symbolic algebraic modeling and analysis techniques applied to the landing gear subsystem in the new Swedish fighter aircraft, JAS 39 Gripen. This is a work in progress report within the larger project COmplex Hybrid SYstems (COHSY) which is a joint project between several academic (Mechanical Engineering, Computer Science and Electrical Engineering) and industrial (Saab Aircraft, Volvo Aeroand VOAC) partners. It is also part of a long term effort within the Automatic Control group in Link oping to deal with discrete dynamic systems, mainly for control applications. Our methods are based on polynomials over finite fields (with Boolean algebra and propositional logic as special cases). Polynomials are used to represent the basic dynamic equations for the processes (controller and plant) as well as static properties of these. Temporal algebra (or temporal logic) is used to represent specifications of system behavior. We use this approach to model the landing g..

The Role of Bowmans Layer in Corneal Regeneration after Phototherapeutic Keratectomy : A Prospective Study Using In Vivo Confocal Microscopy

PURPOSE. To examine the role of Bowmans layer (BL) on the nature of anterior corneal regeneration after excimer laser phototherapeutic keratectomy (PTK). METHODS. A cohort of 13 patients underwent PTK to remove either 7 mu m of BL for treatment of primary recurrent corneal erosions (RCE; six patients) or complete BL removal (15-mu m ablation) to treat RCE or poor vision secondary to map-dot-fingerprint (MDF) dystrophy (seven patients). Clinical examinations and laser-scanning in vivo confocal microscopy (IVCM) were conducted before surgery and at a mean of 4 and 8 months after surgery. RESULTS. Total BL removal resulted in a significant decline in subbasal nerve density at 4 months (P = 0.007) that barely recovered to preoperative levels at 8 months (P = 0.055). With BL partially present, subbasal nerve density did not significantly change from preoperative levels. Superficial, wing, and basal epithelial cell density recovered to preoperative levels within 4 months after PTK, regardless of the presence of BL. Subepithelial keratocytes, however, were more densely distributed in corneas without BL relative to those with a partial BL present (P = 0.005), and increased anterior keratocyte reflectivity was noted in all eyes without BL and in no eye with a partial BL present. CONCLUSIONS. Subbasal nerve regeneration is delayed and subepithelial keratocyte density and reflectivity remain elevated up to 10 months after total BL removal by PTK. The results provide initial evidence for a possible role of BL in facilitating rapid stromal wound healing and an associated recovery of anterior corneal transparency and the restoration of epithelial innervation after epithelial trauma.Original Publication:Neil Lagali, Johan Germundsson and Per Fagerholm, The Role of Bowmans Layer in Corneal Regeneration after Phototherapeutic Keratectomy: A Prospective Study Using In Vivo Confocal Microscopy, 2009, INVESTIGATIVE OPHTHALMOLOGY and VISUAL SCIENCE, (50), 9, 4192-4198.http://dx.doi.org/10.1167/iovs.09-3781Copyright: Research in Vision and Opthalmologyhttp://www.arvo.org