Pseudophakic cystoid macular oedema: 30 months after latanoprost challenge.
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Publications and source records attributed to J E Morgan.
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AIMS: To compare the efficacy of the high specificity Frequency Doubling Technology (FDT) Perimeter Screening Program (C-20-1) to standard threshold automated perimetry in the diagnosis of open-angle glaucoma. METHODS: A total of 100 consecutively presenting patients attending a glaucoma clinic who volunteered for the study (approximately 30% of whom were attending for an initial visit) were examined with the FDT C-20-1 Screening Program and with the Humphrey Field Analyzer (HFA) SITA Fast algorithm and Program 24-2. RESULTS: Of the patients, 17 were excluded due to unreliable visual field results or non-glaucomatous ocular abnormalities. In all, 10 patients were diagnosed as normal, 54 with open-angle glaucoma, eight with ocular hypertension, and 11 as glaucoma suspects. Of the 54 glaucomatous patients, 45 exhibited high-tension glaucoma and nine normal tension glaucoma. Perimetry with the HFA gave a sensitivity of 81.5% for the combined category of glaucoma and glaucoma suspect and a specificity of 83.3% for the combined category of normal and ocular hypertension. Perimetry with the FDT gave a sensitivity of 74.5% and a specificity of 85.2% compared to that of the HFA. CONCLUSION: In the detection of glaucoma, Program C-20-1 of the FDT perimeter exhibits high specificity. It exhibits low sensitivity for the detection of mild loss but high sensitivity for advanced field loss relative to Program 24-2 and the SITA Fast algorithm of the HFA.
PURPOSE: To evaluate the diagnostic power of a novel digital stereoscopic imaging system in the diagnosis of glaucomatous optic neuropathy. DESIGN: Prospective cross-sectional analysis of the diagnostic accuracy of digital stereoscopic optic disc analysis in the diagnosis of glaucomatous optic neuropathy exhibiting mild to moderate field loss. PARTICIPANTS: Fifty-two patients with open-angle glaucoma and 54 normal individuals were recruited. The presence of a reproducible visual field loss characteristic of glaucoma was used as the reference standard for the presence of glaucoma independent of the optic nerve head appearance. Patients were excluded if the optic disc, fundus, or visual field indicated other disease. One eye from each patient and individual was included in the study, the eye with the least field loss and a randomly designated normal eye, respectively. METHODS: Simultaneous stereoscopic optic disc photography was performed on each specified eye. Three experienced observers viewed the resultant stereoscopic image of each nerve head using a Z screen, recorded a subjective clinical diagnosis, and undertook digital stereoscopic planimetry. Separate linear regression analysis was performed, post hoc, from the planimetric results for each observer of the logarithm of neuroretinal rim (NRR) against optic disc area derived from each normal eye. Eyes with NRR areas below the 95th prediction interval of the normal cohort were then classified as glaucomatous. MAIN OUTCOME MEASURES: Sensitivity and specificity for the detection of glaucomatous optic neuropathy. RESULTS: With subjective stereoscopic analysis, sensitivity for glaucoma detection among the 3 observers was 80.8%, 76.9%, and 90.4%, with respective specificities of 94.4%, 79.6%, and 79.6%. Regression analysis of the NRR in 30 degrees segments gave sensitivities between 69.2% and 80.8% and specificities between 83.3% and 90.7%. A combination of the subjective and quantitative analysis did not significantly improve discrimination. CONCLUSIONS: The subjective analysis of digital stereoscopic images provides a useful method for the discrimination of normal and glaucomatous optic nerves. Planimetric analysis does not significantly improve the diagnostic precision of this technique.
PURPOSE: Accurate assessment of the retinal nerve fibre layer (RNFL) is central to the diagnosis and follow-up of glaucoma. The in vivo measurement of RNFL thickness by a variety of digital imaging technologies is becoming an important measure for early detection, as well as for follow-up, of glaucomatous damage. However, when drawing clinical inference concerning the state of the RNFL, it is important to have valid reference data on RNFL thickness in both healthy and diseased eyes. In this review, we summarize the knowledge currently available about RNFL thickness in human and primate eyes. METHODS: A review of the literature on histological analysis of RNFL thickness in the context of glaucomatous damage. CONCLUSIONS: Six studies have so far analysed RNFL thickness. Despite the diverse study methodology taken, a consistent feature of all the data is that the superior and inferior quadrants of the peripapillary retina are thicker than the nasal and temporal quadrants; that the RNFL thickness rapidly diminishes with increasing distance from the disc margin; and that apparently at different locations the ratio of axons to supportive tissue varies significantly. We conclude that limited data are available to describe the normal variation in RNFL thickness in the normal human eye. Further studies may help better characterize the RNFL thickness in health and disease and to facilitate the correlation with clinical methods for nerve fibre layer assessment.
Treatments used for several neurological conditions may adversely affect the eye. Vigabatrin-related retinal toxicity leads to a visual field defect. Optic neuropathy may result from ethambutol and isoniazid, and from radiation therapy. Posterior subcapsular cataract is associated with systemic corticosteroids. Transient refractive error changes may follow treatment with acetazolamide or topiramate, and corneal deposits and keratitis with amandatine. Intraocular pressure can be elevated in susceptible individuals by anticholinergic drugs, including oxybutynin, tolterodine, benzhexol, propantheline, atropine and amitriptyline, and also by systemic corticosteroids and by topiramate. Nystagmus, diplopia and extraocular muscle palsies can occur with antiepileptic drugs, particularly phenytoin and carbamazepine. Ocular neuromyotonia can follow parasellar radiation. Congenital ocular malformations can result from in utero exposure to maternally prescribed sodium valproate, phenytoin and carbamazepine. Neurologists must be aware of potential ocular toxicity of these drugs, and appropriately monitor for potential adverse events.
AIMS: To compare monoscopic and stereoscopic assessment of the optic disc using novel software for the digital stereoscopic analysis of optic disc stereopairs. METHODS: Software was developed for the stereoscopic display of digital optic disc images using an interlaced display method. Neuroretinal rim width was determined at 10 degree intervals around the optic disc using a custom (stereoscopic) cursor whose depth was adjusted to that of Elschnig's rim. Measurements were taken, first viewing the disc monoscopically and at a separate sitting, stereoscopically. RESULTS: Measurements were made in 35 eyes from 35 patients (1260 estimates for each observer) using three observers. The mean cup to disc ratio (CDR) ranged from 0.57 to 0.66 (SD 0.13-0.14) for monoscopic viewing compared with 0.64 to 0.69 (SD 0.12-0.14) for stereoscopic viewing. Stereoscopic assessments gave higher CDRs in temporal, superior, nasal, and inferior aspects of the optic disc (p<0.001, Mann-Whitney U test). Agreement between observers in estimating CDR was high for monoscopic assessment (intraclass correlation coefficient 0.74 (CI 0.72 to 0.76) increasing to 0.80 (0.78 to 0.82) for stereoscopic assessment. CONCLUSION: Digital stereoscopic optic disc assessment provides lower estimates of neuroretinal rim width and higher levels of interobserver agreement compared with monoscopic assessments.
Stem cells, capable of giving rise to both differentiated skeletal muscle and to more stem cells, would be ideal for treating chronic myopathies such as Duchenne Muscular Dystrophy. However, although satellite cells have been shown to be functional muscle stem cells in animal models, other muscle or non-muscle stem cells are far less capable of contributing to skeletal muscle regeneration. This review discusses recent work on stem cell contribution to skeletal muscle regeneration and highlights the problems to be overcome before stem cell treatment of muscle diseases may become a possibility.
Novel ultra-broad bandwidth light sources enabling unprecedented sub-2 microm axial resolution over the 400 nm-1700 nm wavelength range have been developed and evaluated with respect to their feasibility for clinical ultrahigh resolution optical coherence tomography (UHR OCT) applications. The state-of-the-art light sources described here include a compact Kerr lens mode locked Ti:sapphire laser (lambdaC = 785 nm, delta lambda = 260 nm, P(out) = 50 mW) and different nonlinear fibre-based light sources with spectral bandwidths (at full width at half maximum) up to 350 nm at lambdaC = 1130 nm and 470 nm at lambdaC = 1375 nm. In vitro UHR OCT imaging is demonstrated at multiple wavelengths in human cancer cells, animal ganglion cells as well as in neuropathologic and ophthalmic biopsies in order to compare and optimize UHR OCT image contrast, resolution and penetration depth.
Retinal ganglion cells are the output cells of the retina whose axons are under considerable metabolic stress in both health and disease states. They are highly polarised to ensure that mitochondria and enzymes involved in the generation of ATP are strategically concentrated to meet the local energy demands of the cell. In passing from the eye to the brain, axons are protected and supported by glial tissues and the blood supply of the optic nerve head is regulated to maintain the supply of oxygen and nutrients to the axons. In spite of this, the optic nerve head remains the point at which retinal ganglion cell axons are most vulnerable to the effects of increased intraocular pressure or ischaemia. Considerable work has been undertaken in this area to advance our understanding on the pathophysiology of axon damage and to develop new strategies for the prevention of retinal ganglion cell death.
The aim of this study was to optimize human muscle formation in vivo from implanted human muscle precursor cells. We transplanted donor muscle precursor cells (MPCs) prepared from postnatal or fetal human muscle into immunodeficient host mice and showed that irradiation of host muscle significantly enhanced muscle formation by donor cells. The amount of donor muscle formed in cryodamaged host muscle was increased by exposure of donor cells to growth factors before their implantation into injured host muscle. Insulin-like growth factor type I (IGF-I) significantly increased the amount of muscle formed by postnatal human muscle cells, but not by fetal human MPCs. However, treatment of fetal muscle cells with IGF-I, in combination with basic fibroblast growth factor and plasmin, significantly increased the amount of donor muscle formed. In vivo, human MPCs formed mosaic human-mouse muscle fibers, in which each human myonucleus was associated with a zone of human sarcolemmal protein spectrin.
A compact, low-cost, prismless Ti:Al2O3 laser with 176-nm bandwidth (FWHM) and 20-mW output power was developed. Ultrahigh-resolution ophthalmic optical coherence tomography (OCT) ex vivo imaging in an animal model with approximately 1.2-microm axial resolution and in vivo imaging in patients with macular pathologies with approximately 3-microm axial resolution were demonstrated. Owing to the pump laser, this light source significantly reduces the cost of broadband OCT systems. Furthermore, the source has great potential for clinical application of spectroscopic and ultrahigh-resolution OCT because of its small footprint (500 mm x 180 mm including the pump laser), user friendliness, stability, and reproducibility.
AIM: Laser interferometry is a new, non-contact technique for the measurement of axial length. In this study we compared measurements of axial length obtained with this technique with those obtained with ultrasound (A-scan). The reproducibility and examiner-dependency of the two methods were also analysed. METHODS: Patients presenting at the cataract assessment clinic were invited to participate in the study. Axial length measurements were obtained both by contact ultrasound (A-scan) and by non-contact laser interferometry (IOLMasterTM V1.1, Carl Zeiss, Jena, Germany). Intraocular lens powers were calculated using both sets of measurements. The coefficient of variation served as a measure of reproducibility. RESULTS: A total of 100 eyes in 100 patients were evaluated after informed consent had been obtained. Although estimates of axial length obtained with the two techniques were highly correlated, axial lengths obtained with the contact method (mean 23.35 mm, SD 1.81 mm) were consistently lower than those obtained with the non-contact method (mean 23.55 mm, SD 1.76 mm) and the difference was statistically significant (p < 0.001). The coefficient of variation was lower with laser interferometry (0.1%) than with the ultrasound technique (0.49%). CONCLUSIONS: Different estimates of axial length are obtained using contact and non-contact techniques, with the latter producing consistently higher measurements than the former. Laser interferometry provides more reproducible results that should improve the accuracy of measurements of axial length in the clinical setting.
Duchenne's muscular dystrophy (DMD) is a lethal childhood disease caused by mutations of the dystrophin gene, the protein product of which, dystrophin, has a vital role in maintaining muscle structure and function. Homologues of DMD have been identified in several animals including dogs, cats, mice, fish and invertebrates. The most notable of these are the extensively studied mdx mouse, a genetic and biochemical model of the human disease, and the muscular dystrophic Golden Retriever dog, which is the nearest pathological counterpart of DMD. These models have been used to explore potential therapeutic approaches along a number of avenues including gene replacement and cell transplantation strategies. High-throughput screening of pharmacological and genetic therapies could potentially be carried out in recently available smaller models such as zebrafish and Caenorhabditis elegans. It is possible that a successful treatment will eventually be identified through the integration of studies in multiple species differentially suited to addressing particular questions.
BACKGROUND/AIMS: The interpretation of high contrast retinal nerve fibre layer (RNFL) images in glaucoma can be confounded by the presence of image blur; it can be difficult to discern diffuse axon loss in a poor quality image. One solution is to provide an objective measure of the image quality based on features in the image other than the RNFL. In this study the authors have developed an objective method to quantify the clarity of RNFL images, comparing it with a subjective image grading system. METHODS: Digitally acquired, monochrome retinal images were taken from 58 eyes (one image per eye) with a Topcon 50 IX retinal camera. Image resolution was 1320 x 1032 pixels at 8 bits per pixel. Image sharpness was subjectively graded by two masked experienced observers on a scale 1 to 5 relative to a reference set of RNFL images. Software algorithms were developed using Matlab (5.2) to calculate the acutance, an objective measure of the physical characteristics that underlie the subjective impression of sharpness in an image. RESULTS: Acutance values could be calculated for all the images. The Pearson correlation coefficients of the log of the acutance for each image and the subjective grades of observer 1 and observer 2 were 0.90 (p<0.001, n=58) and 0.84 (p<0.001, n=58) respectively. CONCLUSIONS: These data suggest that acutance may provide a useful objective measure of image quality, which correlates well with the subjective impression of the digital retinal image sharpness. Objective measures of image quality should help in the discrimination of diffuse retinal nerve fibre loss from image blur in patients with diffuse glaucomatous damage.
SUMMARY: There has been some debate concerning the selective loss of retinal ganglion cells belonging to the magnocellular pathway in early glaucoma. Although histologic studies of retinal ganglion cells in experimental and human glaucoma have suggested selective loss of the larger cells and, by implication, selective damage to the magnocellular pathway, this has not been confirmed using psychophysical tests. Recent studies of retinal ganglion cell morphology in experimental glaucoma provide evidence that retinal ganglion cells undergo morphologic changes prior to cell death; cell volume is reduced in surviving cells with corresponding reductions in the size of the axon and dendritic tree. The magnitude of these changes is consistent with cell shrinkage as an explanation for the apparent selective damaged reported in earlier studies. It is also likely that widespread changes in the retinal ganglion cell population precede cell death, which will affect the physiologic behavior of these cells.
AIM: The psychophysical evaluation of selective cell loss in early glaucoma and ocular hypertension. METHODS: Contrast sensitivity was measured for the detection of luminance modulated gratings at a range of spatial (0.5, 2, 8 c/deg) and temporal (0, 16 Hz) frequency combinations in three groups of age matched patients (primary open angle glaucoma, ocular hypertension, normal controls; n=16). Stimuli of 5 degrees were presented foveally and at 15 degrees along the nasal horizontal meridian under photopic conditions. RESULTS: Fovea: Compared to the normal group, the thresholds for the glaucoma patients were significantly elevated at all spatial and temporal frequencies (p<0.0001), but this reduction was not significantly different at any particular spatial or temporal frequency (p>0.1). There was no difference in contrast sensitivity between the normals and OHTs (p>0.10). Periphery: The thresholds of the glaucoma patients were elevated compared to the normal controls (p<0.01). The loss of sensitivity was slightly greater at the higher spatial frequencies for both stationary and flickering patterns but this did not reach significance (p=0.09). The contrast sensitivity in normal and OHT groups was not significantly different (p>0.10). CONCLUSIONS: In early glaucoma, the reduction in contrast sensitivity to stimuli which isolate the magnocellular pathway (0.5 c/deg, 16 Hz) was not significantly different compared with the reduction in contrast sensitivity to stimuli that isolate the parvocellular pathway. These findings are not consistent with the hypothesis that the magnocellular pathway is selectively damaged in early glaucoma.
Advances in our understanding of the pathophysiology of retinal ganglion cell death in glaucoma are providing important insights into the functional changes occurring in retinal ganglion cells in the early stages of the disease. These exciting new findings may help us develop psychophysical tests to monitor early retinal ganglion cell damage, possibly before neurons are committed to the process of cell death.