Early posterior vitreous detachment is associated with LAMA5 dominant mutation

Background: Extracellular matrix molecular components, previously linked to multisystem syndromes include collagens, fibrillins and laminins. Recently, we described a novel multisystem syndrome caused by the c.9418G>A p.(V3140M) mutation in the laminin alpha-5 (LAMA5) gene, which affects connective tissues of all organs and apparatus in a three generation family. In the same family, we have also reported a myopic trait, which, however, was linked to the Prolyl 4-hydroxylase subunit alpha-2 (P4HA2) gene. Results of investigation on vitreous changes and their pathogenesis are reported in the present study.Materials and Methods: Nineteen family individuals underwent complete ophthalmic examination including best-corrected visual acuity (BCVA), fundus examination, fundus photography, intraocular pressure measurement, axial length measurement using ocular biometry, Goldmann visual field examination, standard electroretinogram, SD-OCT. Segregation analysis of LAMA5 and P4HA2 mutations was performed in enrolled members.Results: The vitreous alterations fully segregated with LAMA5 mutation in both young and adult family members. Slight reduction of retinal thickness and peripheral retinal degeneration in only two patients were reported.Conclusions: In this work we showed that PVD is a common trait of LAMA5 multisystem syndrome, therefore occurring as an age-unrelated trait. We hypothesize that the p.(V3140M) mutation results in a reduction of retinal inner limiting membrane (ILM) stability, leading to a derangement in the macromolecular structure of the vitreous gel, and PVD. Further investigations will be necessary to elucidate the role of wild type and mutated LAMA5 in the pathogenesis of PVD.     

Successful Treatment for BK Virus Nephropathy by Leflunomide in a Kidney Transplant Patient: A Case Report

IntroductionThe immunosuppressant agents in kidney transplantation (KT) may lead to various complications such as opportunistic infections and malignancies. BK virus associated nephropathy is a significant complication following KT, and it can result in graft failure. BK virus causes tubulointerstitial nephritis, ureter stenosis, and even graft failure in KT recipients with impaired immune system. We described a 63-year-old woman, who was a hepatitis C carrier and on dialysis for 22 years before KT, who received cadaveric-donor KT 2 years previously. She reported decreasing urine output and general weakness. The serum creatinine level was slightly increased from 2.94 to 4.38 mg/dL.MethodsImmunosuppressant medications including prednisolone, everolimus, cyclosporin, and mycophenolate sodium were continued as maintenance therapy post KT. Kidney biopsy was performed due to deterioration of graft function.ResultsThe kidney biopsy showed consistent results with early-stage polyomavirus nephropathy, characterized by focal viral cytopathic changes with positive immunohistochemical signals and mesangial proliferative glomerulonephritis, immune-complex-mediated (Fig 1 and Fig 2). Negative C4d staining at peritubular capillary was reported. The dosage of mycophenolate sodium was tapered from 720 to 360 mg daily and that of everolimus increased from 0.5 to 1.0 mg daily due to BK viral infection with BK nephropathy. The serum creatinine level was 2.75 mg/dL after treatment.ConclusionEarly detection of BK nephropathy and decreasing immunosuppressant agents are the mainstay of treatment. Substituting leflunomide for mycophenolate sodium and increasing dosage of everolimus has been proposed to solve BK nephropathy. We presented that the use of leflunomide in such situation is in a timely manner.     

Robust rigid registration of retinal angiograms through optimization

Retinal fundus photographs are employed as standard diagnostic tools in ophthalmology. Serial photographs of the flow of fluorescein and indocyanine green (ICG) dye are used to determine the areas of the retinal lesions. For objective measurements of features, the registration of the images is a necessity. In this paper, we employ optimization techniques for registration with the help of 2-parameter translational motion model of retinal angiograms, based on non-linear pre-processing (Wiener filtering and morphological gradient) and computation of the similarity criteria for the alignment of the two gradient images for any given rigid transformation. The optimization methods are effectively employed to minimize the similarity criterion.

The presence of noise, the variations in the background and the temporal variation of the fluorescence level pose serious problems in obtaining a robust registration of the retinal images. Moreover, local search strategies are not robust in the case of ICG angiograms, even if one uses a multiresolution approach.

The present work makes a systematic comparison of different optimization techniques, namely the minimization method derived from the optical flow formulation, the Nelder-Mead local search and the HCIAC ant colony metaheuristic, each optimizing a similarity criterion for the gradient images. The impact of the resolution and median filtering of gradient image is studied and the robustness of the approaches is tested through experimental studies, performed on macular fluorescein and ICG angiographies.

Our proposed optimization techniques have shown interesting results especially for high resolution difficult registration problems. Moreover, this approach seems promising for affine (6-parameter motion model) or elastical registrations.     

Vehicle of triamcinolone acetonide is associated with retinal toxicity and transient increase of lens density

Background Intravitreal triamcinolone acetonide (TA) has been widely used as a therapeutic method for many ocular diseases, but a consensus on an appropriate safe therapeutic window of dosage for intravitreal injection, and whether vehicle of TA should be reduced or eliminated, has not yet been reached. The aim of this article is to investigate these issues.Methods Forty New Zealand white rabbits were divided into four experimental groups and one control group. Four or 25 mg TA, with vehicle either reduced or not, was injected into the vitreous cavity of rabbits in experimental groups. Rabbits in the control group received 0.2 ml intravitreal sterile saline solution. Intraocular pressures (IOP) were measured by a Tonopen tonometer. Values of lens density were measured by a Pentacam system. Soluble protein, total antioxidation capacity, reduced glutathione (GSH), glutathion peroxidase (GSH-px), and superoxide dismutase (SOD) in lens were measured by specific kits. ERG and pathological examinations, including light and electron microscopy of the retina, were also performed.Results Elevation of IOP was noted in all experimental groups after intravitreal TA (P<0.01, paired t-test). Significant increase of lens density was noticed at 1 week after intravitreal TA in the 25 mg vehicle-containing group (P<0.0001, paired t-test). Significant loss of GSH-px activity was noticed at the end of the study (P<0.05, paired t-test), while SOD activity increased (P<0.05, paired t-test). Amplitudes of ERG waves declined significantly in vehicle-containing groups (P<0.01, paired t-test) at the end of the study. Pathological examination showed obvious retinal toxicity in vehicle-containing groups.Conclusions Vehicle of TA should be eliminated or reduced before intravitreal injection to avoid potential retinal toxicity and transient increase in lens density.Presented at Chinese Academy of Fundus Disease Meeting, April, 2005.This study was supported by the 985 Fund of Peking University, Beijing.The authors have no financial interest in any instruments or drugs mentioned in this study.     

Diagnostic accuracy of the Retinal Thickness Analyser: differentiation between normal eyes and eyes with glaucoma or macular pathologies

Background The Retinal Thickness Analyser (RTA) is intended to detect glaucomatous changes as well as macular pathologies at the posterior pole. We determined the diagnostic accuracy for eyes with manifest glaucoma or macular diseases.Methods We examined 71 eyes with long-term, established eye conditions. Included were 28 eyes with glaucoma, 21 with different macular diseases and 22 normal eyes. All examinations were evaluated in a blind-test by RTA experts without any clinical information on the patients. After comparison of the RTA interpretation with the clinical diagnosis, we determined sensitivity, specificity, positive and negative predictive values.Results Of 71 examinations, 15 (21%) were not interpretable. If these results are excluded, the following diagnostic accuracy values were calculated for glaucoma and macular disorders respectively: sensitivity 75 and 59%, specificity 55 and 97%, positive predictive value 48 and 90% and negative predictive value 80 and 84%. These values were not significantly different when both eyes of each patient were included in the final analysis (n=133).Conclusion The diagnostic values of the RTA determined in this case control study were not satisfactory. However, no clinical information was used in the assessment. The extent to which additional clinical information increases the diagnostic value remains to be determined.     

Ocular changes in the mouse embryo following acute maternal ethanol intoxication

The development of the eye was investigated in the mouse embryo following a single administration of ethanol plus [3H]thymidine to the dam on day 13 of gestation. After 1 hr there was no difference in the number of labelled cells/100 micron 2 in the neural layer of the retina compared to controls, but there was an alcohol-related reduction in labelling density. After 24 hr there was an increase in the numbers of both pyknotic cells and mitotic figures, breaks occurred in the inner surface of the retina and cell debris was being extruded into the posterior chamber. At 48 hr the increase in pyknotic cells persisted, but there was less evidence of cell debris and the borders had been repaired. The estimated cell cycle time in the neural progenitor cells following maternal alcohol administration was increased 7-fold compared to controls. Morphometric analysis revealed that after 48 hr there were significant alcohol-related reductions in the width and depth of the eye, in the thickness of the neural layer and in the interocular distance. It appears that many of the ophthalmic abnormalities reported in human fetal alcohol syndrome can be produced in the mouse embryo following a single episode of acute maternal intoxication during a critical period of ocular ontogeny, and that they evolve primarily from disturbances in the normal patterns of recruitment and loss of neural progenitor cells in the developing retina.     

降糖灵1号降血糖的实验研究

目的　验证降糖灵 1号的降血糖作用。方法　以大、小白鼠为实验动物 ,分别与空白对照、高血糖对照及降糖甲片组和消渴丸组进行对照。研究降糖灵 1号对肾上腺素性和四氧嘧啶性高血糖的药理作用。结果　降糖灵 1号组除与消渴丸组对糖尿病差异无显著性意义 (P >0 0 5 )外 ,与其他各组差异均有显著性意义 (P <0 0 5 ,P <0 0 1)。结论　降糖灵 1号具有明显的降血糖作用     

妊高征与眼底视网膜病变的临床探讨

目的 :探讨妊高征患者临床特征与视网膜病变的关系。方法 :观察 2 2 0例妊高征患者的眼底情况。结果 :视网膜病变与水肿关系不密切 ,与平均动脉压、蛋白尿的严重程度、病程及红细胞压积有密切关系 ;有眼底改变者 118例 ,占 5 0 .3%。结论 :眼底镜检查是临床上借以了解视网膜血管的常用方法 ,并可反映妊高征病情的程度 ,为产程处理提供依据