Acute Herpetic Keratitis: What is the Role for Ganciclovir Ophthalmic Gel?

Herpes simplex keratitis (HSK) is a major cause of corneal blindness in the world. Following the primary infection, the virus enters into a latent phase. Recurrent infectious or immune keratitis cause structural damage to the cornea, scarring, and may lead to blindness. Several commercially available topical and oral antiviral drugs for HSK are currently available. However, toxicity and low patient compliance hamper their use in HSK. Further, oral antiviral drugs alone are not always effective in HSK. Thus, there had been a need for safe and effective topical antiviral agents against HSK. Systemic ganciclovir has been in use for the treatment of cytomegalovirus infections. Recently, topical ganciclovir has become available for use in patients with HSK. Ganciclovir 0.15% ophthalmic gel has been shown to be both safe and effective against viruses of the herpes family. Topical ganciclovir ophthalmic gel is well tolerated and does not cause significant toxic effects on the ocular surface. Several multicenter studies have revealed the potential role of ganciclovir ophthalmic gel in the treatment and prophylaxis of epithelial HSK. In this paper, we have reviewed the pharmacology, efficacy, side effects, and the role of ganciclovir ophthalmic gel 0.15% in the treatment of acute herpetic keratitis

Corneal Allograft Rejection: Immunopathogenesis to Therapeutics

Corneal transplantation is among the most successful solid organ transplants. However, despite low rejection rates of grafts in the ‘low-risk’ setting, rejection can be as high as 70% when grafted into ‘high-risk’ recipient beds. Under normal homeostatic conditions, the avascular cornea provides a unique environment that facilitates immune and angiogenic privilege. An imbalance in pro-inflammatory, angiogenic and lymphangiogenic mediators leads to a breakdown in corneal immune privilege with a consequent host response against the donor graft. Recent developments in lamellar and endothelial keratoplasties have reduced the rates of graft rejection even more, while providing improved visual outcomes. The corneal layer against which an immune response is initiated, largely determines reversibility of the acute episode. While epithelial and stromal graft rejection may be treated with topical corticosteroids with higher success, acute endothelial rejection mandates a more aggressive approach to therapy due to the lack of regenerative capacity of this layer. However, current immunosuppressive regimens come with the caveat of ocular and systemic side effects, making prolonged aggressive treatment undesirable. With the advent of biologics, efficacious therapies with a superior side effect profile are on the horizon. In our review we discuss the mediators of ocular immune privilege, the roles of cellular and molecular immune players in graft rejection, with a focus on human leukocyte antigen and antigen presenting cells. Furthermore, we discuss the clinical risk factors for graft rejection and compare rates of rejection in lamellar and endothelial keratoplasties to traditional penetrating keratoplasty. Lastly, we present the current and upcoming measures of therapeutic strategies to manage and treat graft rejection, including an overview of biologics and small molecule therapy

Two-dimensional plane for multi-scale quantification of corneal subbasal nerve tortuosity

Purpose To assess the performance of a novel system for automated tortuosity estimation and interpretation. Methods: A supervised strategy (driven by observers' grading) was employed to automatically identify the combination of tortuosity measures (i.e., tortuosity representation) leading to the best agreement with the observers. We investigated 18 tortuosity measures including curvature and density of inflection points, computed at multiple spatial scales. To leverage tortuosity interpretation, we propose the tortuosity plane (TP) onto which each image is mapped. Experiments were carried out on 140 images of subbasal nerve plexus of the central cornea, covering four levels of tortuosity. Three experienced observers graded each image independently. Results: The best tortuosity representation was the combination of mean curvature at spatial scales 2 and 5. These tortuosity measures were the axes of the proposed TP (interpretation). The system for tortuosity estimation revealed strong agreement with the observers on a global and per-level basis. The agreement with each observer (Spearman's correlation) was statistically significant (αs = 0.05, P < 0.0001) and higher than that of at least one of the other observers in two out of three cases (ρOUR = 0.7594 versus ρObs3 = 0.7225; ρOUR = 0.8880 versus ρObs1 = 0.8017, ρObs3 = 0.7315). Based on paired-sample t-tests, these improvements were significant (P < 0.001). Conclusions: Our automated system stratifies images by four tortuosity levels (discrete scale) matching or exceeding the accuracy of experienced observers. Of importance, the TP allows the assessment of tortuosity on a two-dimensional continuous scale, thus leading to a finer discrimination among images

Bilateral Nerve Alterations in a Unilateral Experimental Neurotrophic Keratopathy Model: A Lateral Conjunctival Approach for Trigeminal Axotomy

To study bilateral nerve changes in a newly developed novel mouse model for neurotrophic keratopathy by approaching the trigeminal nerve from the lateral fornix. Surgical axotomy of the ciliary nerve of the trigeminal nerve was performed in adult BALB/c mice at the posterior sclera. Axotomized, contralateral, and sham-treated corneas were excised on post-operative days 1, 3, 5, 7 and 14 and immunofluorescence histochemistry was performed with anti-β-tubulin antibody to evaluate corneal nerve density. Blink reflex was evaluated using a nylon thread. The survival rate was 100% with minimal bleeding during axotomy and a surgical time of 8±0.5 minutes. The blink reflex was diminished at day 1 after axotomy, but remained intact in the contralateral eyes in all mice. The central and peripheral subbasal nerves were not detectable in the axotomized cornea at day 1 (p<0.001), compared to normal eyes (101.3±14.8 and 69.7±12.0 mm/mm2 centrally and peripherally). Interestingly, the subbasal nerve density in the contralateral non-surgical eyes also decreased significantly to 62.4±2.8 mm/mm2 in the center from day 1 (p<0.001), but did not change in the periphery (77.3±11.7 mm/mm2, P = 0.819). Our novel trigeminal axotomy mouse model is highly effective, less invasive, rapid, and has a high survival rate, demonstrating immediate loss of subbasal nerves in axotomized eyes and decreased subbasal nerves in contralateral eyes after unilateral axotomy. This model will allow investigating the effects of corneal nerve damage and serves as a new model for neurotrophic keratopathy

Discrete-time Stable Geometric Controller and Observer Designs for Unmanned Vehicles

In the first part of this dissertation, we consider tracking control of underactuated systems on the tangent bundle of the six-dimensional Lie group of rigid body motions, SE(3). We formulate both asymptotically and finite-time stable tracking control schemes for underactuated rigid bodies that have one translational and three rotational degrees of freedom actuated, in discrete time. Rigorous stability analyses of the tracking control schemes presented here guarantee the nonlinear stability of these schemes. The proposed schemes here are developed in discrete time as it is more convenient for onboard computer implementation and ensures stability irrespective of the sampling period. A stable convergence of translational and rotational tracking errors to the desired trajectory is guaranteed for both asymptotically and finite-time stable schemes. In the second part, a nonlinear finite-time stable attitude estimation scheme for a rigid body that does not require knowledge of the dynamics is developed. The proposed scheme estimates the attitude and constant angular velocity bias vector from a minimum of two known linearly independent vectors for attitude, and biased angular velocity measurements made in the body-fixed frame. The constant bias in angular velocity measurements is also estimated. The estimation scheme is proven to be almost globally finite-time stable in the absence of measurement errors using a Lyapunov analysis. In addition, the behavior of this estimation scheme is compared with three state-of-the-art filters for attitude estimation, and the comparison results are presented

Effects of Omega-3 Supplementation on Exploratory Outcomes in the Dry Eye Assessment and Management Study.

We report results from a multicenter, randomized clinical trial (N=535) of the effect of ω-3 supplementation, relative to placebo, on exploratory and minimally invasive outcome measures for moderate to severe dry eye disease

Impact of Airflow Limitation on Carotid Atherosclerosis in Coronary Artery Disease Patients

名古屋大学Nagoya University博士(医学)doctoral thesi

METODE QUALITY FUNCTION DEPLOYMENT (QFD) UNTUK INFORMASI PENYEMPURNAAN PERAKITAN VARIETAS MELON

Problems faced by the development of melon fruit in Indonesia are closely related to the domestic availability of seed. Although the government research center as well as private seed producers have been able to produce melon seed, the largest part of the seed supply is still imported. The objectives of this study are to pursue or to identify ideotype of melon that the domestic consumers is willing to consume and to apply QFD methods (to compose HOQ matrix) in developing domestic melon seed breeding.The melon fruit demanded by institutional consumers is the melon fruit without net, and demanded melon fruit by the final consumers is the netted melon fruit. The application of QFD in the planning of the melon varieties is started by composing the HOQ matrix that consisted of the following steps: first, to compose the customers conditions; second, to compose the technical conditions; third, to develop the relationship between the customers and technical condition; fourth, to evaluate the technical competitiveness; fifth, to develop the technical conditions; sixth, to develop the customers condition, and finally, to develop the priority of technical conditions. The recommendation given to the melon seed breeders is to concentrate on the technical conditions with the highest absolute and relative weighted values

Bilateral Posterior Ischemic Optic Neuropathy in a Patient with Severe Diabetic Ketoacidosis

Purpose: To report a case of bilateral posterior ischemic optic neuropathy (PION) in a patient with severe diabetic ketoacidosis (DKA). Design: Observational case report. Participant: A 35-year-old male who suffered bilateral visual loss during a severe episode of DKA. Methods: Neuro-ophthalmological examination, neuroimaging consisting of a CT scan and MRI of the brain and orbits, as well as a MRA of brain vessels. Results: Bilateral PION was diagnosed in a 35-year-old male with no light perception vision, who emerged from a coma caused by severe DKA. The patient developed optic nerve pallor in both eyes 4 weeks after the initial examination. Visual acuity with no light perception in both eyes remained unchanged after 6 months' follow-up. Conclusions: Severe DKA can be complicated by bilateral PION, resulting in total blindness