TL;DR: A clinically useful map that relates visual field test points to regions of the optic nerve head (ONH) has been produced that will aid clinical evaluation of glaucoma patients and suspects, as well as form the basis for investigations of the relationship between retinal light sensitivity and ONH structure.
TL;DR: Interruption of BDNF retrograde transport and accumulation of TrkB at the optic nerve head in acute and chronic glaucoma models suggest a role for neurotrophin deprivation in the pathogenesis of RGC death in glau coma.
Abstract: Purpose In both animal model system and in human glaucoma, retinal ganglion cells (RGCs) die by apoptosis. To understand how RGC apoptosis is initiated in these systems, the authors studied RGC neurotrophin transport in experimental glaucoma using acute intraocular pressure (IOP) elevations in rats and chronic IOP elevation and unilateral optic nerve transections in monkeys. Methods Eyes were studied in masked fashion by light and electron microscopy and by immunohistochemistry with antibodies directed against the tyrosine kinase receptors (TrkA, B, and C) and against brain-derived neurotrophic factor (BDNF), as well as by autoradiography to identify retrograde axonal transport of 125I-BDNF injected into the superior colliculus. Results With acute glaucoma in the rat, RGC axons became abnormally dilated, accumulating vesicles presumed to be moving in axonal transport at the optic nerve head. Label for TrkB, but not TrkA, was relatively increased at and behind the optic nerve head with IOP elevation. Abnormal, focal labeling for TrkB and BDNF was identified in axons of monkey optic nerve heads with chronic glaucoma. With acute IOP elevation in rats, radiolabeled BDNF arrived at cells in the RGC layer at less than half the level of control eyes. Conclusions Interruption of BDNF retrograde transport and accumulation of TrkB at the optic nerve head in acute and chronic glaucoma models suggest a role for neurotrophin deprivation in the pathogenesis of RGC death in glaucoma.
TL;DR: Retinal nerve fiber layer was significantly thinner in glaucomatous eyes than in ocular hypertensive and normal eyes throughout 360 degrees and in all quadrants.
Abstract: Objective To quantitatively assess and compare the thickness of the retinal nerve fiber layer (RNFL) in ocular hypertensive eyes with normal and glaucomatous eyes using the Optical Coherence Tomograph (OCT 2000, software version A4X1; Humphrey Instruments, San Leandro, Calif). Methods The mean RNFL thickness of ocular hypertensive (n = 28) eyes was compared with age-matched normal (n = 30) and glaucomatous (n = 29) eyes. Subject eyes were classified into diagnostic groups based on intraocular pressure, stereoscopic disc photographs, and standard automated perimetry. Three circular scans were obtained for each eye at a diameter of 3.4 mm around the optic disc. In each eye, average RNFL thickness measurements were obtained in temporal, superior, nasal, and inferior quadrants. A single index of average RNFL thickness throughout 360° also was obtained. Results Mean (95% confidence interval) RNFL was significantly thinner in ocular hypertensive eyes than in normal eyes, 72.8 µm (66.4-78.1 µm) and 85.8 µm (80.2-91.7 µm), respectively. More specifically, RNFL was significantly thinner in ocular hypertensive eyes than in normal eyes in the inferior quadrant, 84.8 µm (75.6-94.0 µm) vs 107.6 µm (99.3-115.9 µm); and in the nasal quadrant, 44.1 µm (37.5-51.7 µm) vs 61.8 µm (53.0-65.6 µm). Retinal nerve fiber layer was significantly thinner in glaucomatous eyes than in ocular hypertensive and normal eyes throughout 360° and in all quadrants. Conclusion These findings suggest that quantitative differences in RNFL thickness exist between age-matched ocular hypertensive, normal, and glaucomatous eyes.
TL;DR: The overall prevalence of OAG in the present study was comparable to most population-based studies, however, prevalence figures differed by a factor of 12 when their criteria for OAG were applied to this population.
Abstract: Purpose To create a quantitative basis for diagnostic criteria for open-angle glaucoma (OAG), to propose an epidemiologic definition for OAG based on these, and to determine the prevalence of OAG in a general white population. Methods Of the 7983 subjects 55 years of age or older participating in the population-based Rotterdam Study, 6756 subjects participated in the ophthalmic part of this study (6281 subjects living independently and 475 in nursing homes). The criteria for the diagnosis of OAG were based on ophthalmoscopic and semiautomated Imagenet estimations of the optic disc such as vertical cup-to-disc ratio (VCDR), minimal width of neural rim, or asymmetry in VCDR between both eyes, and visual field testing with kinetic Goldmann perimetry. All criteria for the diagnosis of OAG were assessed in a masked way independently of each other. Results Mean VCDR on ophthalmoscopy was 0.3 and with Imagenet 0.49, and the 97.5th percentile for both was 0.7. The prevalence of glaucomatous visual field defects was 1.5%. Overall prevalence of definite OAG in the independently living subjects was 0.8% (95% confidence interval [CI] 0.6, 1.0; 50 cases). Prevalence of OAG in men was double that in women (odds ratio 2.1; 95% CI 1.2, 3.6). Different commonly used criteria for diagnosis of OAG resulted in prevalence figures ranging from 0.1% to 1.2%. Conclusions The overall prevalence of OAG in the present study was comparable to most population-based studies. However, prevalence figures differed by a factor of 12 when their criteria for OAG were applied to this population. A definition for definite OAG is proposed: a glaucomatous optic neuropathy in eyes with open angles in the absence of history or signs of secondary glaucoma characterized by glaucomatous changes based on the 97.5 percentile for this population together with glaucomatous visual field loss. In the absence of the latter or of a visual field test, it is proposed to speak of probable OAG based on the 99.5th or possible OAG based on the 97.5th percentiles of glaucomatous disc changes for a population under study.
TL;DR: Initial finite element models show that IOP-related stress within the load-bearing connective tissues of the optic nerve head is substantial even at low levels of IOP.
Abstract: Purpose To study the relationship between intraocular pressure (IOP) and the IOP-related stress (force/cross-sectional area) it generates within the load-bearing connective tissues of the optic nerve head Methods Thirteen digital, three-dimensional geometries were created representing the posterior scleral shell of 13 idealized human eyes Each three-dimensional geometry was then discretized into a finite element model consisting of 900 constituent finite elements In five models, the scleral canal was circular (diameters of 050, 150, 175, 200, and 256 mm), with scleral wall thickness (08 mm) and inner radius (120 mm) held constant In three models, the canal was elliptical (vertical-to-horizontal ratios of 2:1 [250 x 125 mm], 15:1 [21 x 14 mm], and 115:1 [192 x 167 mm]), with the same constant scleral wall thickness and inner radius In five additional models, scleral canal size was held constant (192 x 167 mm), and either scleral wall thickness (three models, 05, 10, and 15 mm) or inner radius (two models, 130 and 140 mm) was varied In all models, each finite element was assigned a single isotropic material property, either scleral (modulus of elasticity, 5500 kPa) or axonal (modulus of elasticity, 55 kPa) Maximum stresses within specific regions were calculated at an IOP of 15 mm Hg (2000 Pa) Results Larger scleral canal diameter, elongation of the canal, and thinning of the sclera increased IOP-related stress for a given level of IOP For all models, maximum IOP-related stress ranged from 6 x IOP (posterior sclera) to 122 x IOP (laminar trabeculae) For each model, maximum IOP-related stress was highest within the laminar trabecular region and decreased progressively through the laminar insertion, peripapillary scleral, and posterior scleral regions Varying the inner radius had little effect on the maximum IOP-related stress within the scleral canal Conclusions Initial finite element models show that IOP-related stress within the load-bearing connective tissues of the optic nerve head is substantial even at low levels of IOP Although the data suggest that scleral canal size and shape and scleral thickness are principal determinants of the magnitude of IOP-related stress within the optic nerve head, models that incorporate physiologic scleral canal and laminar geometries, a more refined finite element model meshwork, and nonisotropic material properties will be required to confirm these results
TL;DR: This technique has a highlevel of sensitivity to detect changes in the optic disc while maintaining a high level of specificity and the number of significant test results in the patient with progressive glaucoma decreased after correction for spatial correlation, the change was readily apparent.
Abstract: PURPOSE. To describe and evaluate a new statistical technique for detecting topographic changes in the optic disc and peripapillary retina measured with confocal scanning laser tomography. METHODS. The 256 × 256-pixel array of topographic height values obtained with each image from the Heidelberg Retina Tomograph (Heidelberg Engineering, Heidelberg, Germany) was divided into an array of 64 × 64 superpixels, where each superpixel contained 16 (i.e., 4 × 4) pixels. An analysis of variance technique was developed to analyze each superpixel with three baseline and three follow-up images. The performance of the technique was tested with and without adjustment for spatial correlation of topographic values using computer simulations and with real data from a normal control subject and a patient with progressive glaucomatous disc change. RESULTS. Computer simulation with fixed population means and variance, and varying spatial correlation showed a monotonically increasing number of superpixels with significant test results (false positives), with 20% false-positives when the spatial correlation was 0.8 (the approximate median value in real patient data). The number of false-positive results was similar (17%) in serial images of a normal subject. When corrected for spatial correlation, the number of false-positives was independent of the level of spatial correlation and remained at the expected value of less than 5% in both simulations and real data. Although the number of significant test results in the patient with progressive glaucoma decreased after correction for spatial correlation, the change was readily apparent. Statistical power to detect mean differences in topographic values ranging from 0.5 to 4.0 SDs in computer simulation showed low power for changes of 1 SD or less, but increased dramatically with larger changes. CONCLUSIONS. This technique has a high level of sensitivity to detect changes in the optic disc while maintaining a high level of specificity.
TL;DR: Optic nerve head and retinal responses, including the depletion of endogenous neurotrophins, are readily identified in the rat eye after experimental IOP elevation, suggesting that the withdrawal of neurotrophic support was not the only determinant of retinal ganglion cell apoptosis and axonal degeneration in response to pressure.
Abstract: Purpose To determine the chronology of optic nerve head and retinal responses to elevated intraocular pressure (IOP) Methods After 1 to 39 days of unilaterally elevated IOP, experimental and fellow rat eyes were examined for morphology and immunohistochemical labeling alterations and for ganglion cell DNA fragmentation Results Mean IOP for the experimental eyes was 36 +/- 8 mm Hg, an approximately 15-mm Hg elevation above normal values By 7 days of pressure elevation above 40 mm Hg, endogenous immunostaining for brain-derived neurotrophic factor and neurotrophin 4/5 was absent from the nerve head and superior retina, whereas normal labeling was present in the inferior retina and distal optic nerve of these same eyes These changes were preceded by a loss of gap junctional connexin43 labeling and astrocytic proliferation in the nerve head and by increased retinal ganglion cell layer apoptosis in the retina Nerve head depletion of neurotrophins coincided with evidence of axonal degeneration, loss of astrocytic glial fibrillary acidic protein staining, and spread of collagen VI vascular immunolabeling After longer durations at these same pressures, neurotrophin labeling returned to nerve head glia and scattered retinal ganglion cells Conclusions Optic nerve head and retinal responses, including the depletion of endogenous neurotrophins, are readily identified in the rat eye after experimental IOP elevation However, the apparent chronology of these responses suggests that the withdrawal of neurotrophic support was not the only determinant of retinal ganglion cell apoptosis and axonal degeneration in response to pressure
TL;DR: The increased immunostaining of HSP 60 and HSP 27 in the glaucomatous eyes may reflect a role of these proteins as a cellular defense mechanism in response to stress or injury inglaucoma.
Abstract: Purpose To examine immunostaining of 60-kd and 27-kd heat shock proteins (HSP 60 and HSP 27), which are known to increase cell survival in response to stress, in glaucomatous retina and optic nerve head. Methods Six postmortem eyes from patients with primary open-angle glaucoma, 6 eyes from patients with normal-pressure glaucoma, and 6 eyes from age-matched normal subjects were studied by immunohistochemistry. The sections of the retina and optic nerve head were examined after immunostaining with antibodies to HSP 60 and HSP 27. Results The intensity of the immunostaining and the number of labeled cells for heat shock proteins (HSPs) were greater in retina sections from glaucomatous eyes than in sections from normal eyes from age-matched donors. Retinal immunostaining of HSP 60 was prominent in the retinal ganglion cells and photoreceptors, whereas immunostaining of HSP 27 was prominent in the nerve fiber layer and ganglion cells as well as in the retinal vessels. In addition, retinal immunostaining of these HSPs exhibited regional and cellular differences. Optic nerve heads of glaucomatous eyes exhibited increased immunostaining of HSP 27, but not HSP 60, which was mostly associated with astroglial cells in the lamina cribrosa. Conclusion The increased immunostaining of HSP 60 and HSP 27 in the glaucomatous eyes may reflect a role of these proteins as a cellular defense mechanism in response to stress or injury in glaucoma. Clinical Relevance These findings suggest that immunoregulation is an important component of glaucomatous optic neuropathy.
TL;DR: Clinical factors that best predicted poor visual acuity were increasing tumor thickness, proximity to foveola of less than 5 mm, notched plaque shape, tumor recurrence, patient age 60 years or older, subretinal fluid, and diabetes mellitus or hypertension.
Abstract: Objective To identify clinical predictive factors for visual outcome in a large series of patients who underwent plaque radiotherapy for uveal melanoma. Design Clinical factors, including patient data, tumor features, and radiation variables, were analyzed for their impact on visual acuity using Cox proportional hazards regression models. Participants Patients with uveal melanoma and initial visual acuity of 20/100 or better in the affected eye who were treated with plaque radiotherapy between July 1976 and June 1992. Main Outcome Measures Two end points were used to evaluate posttreatment visual acuity: (1) final visual acuity (good [20/20-20/100] vs poor [20/200 to no light perception]) and (2) loss of visual acuity (minimal [ Results Of 1300 consecutive patients with uveal melanoma treated by plaque radiotherapy, 1106 had a visual acuity of 20/100 or better at the time of treatment. In this group, poor visual acuity was found in 34% at 5 years and 68% at 10 years of follow-up. From multivariable analysis, clinical factors that best predicted poor visual acuity were increasing tumor thickness, proximity to foveola of less than 5 mm, notched plaque shape, tumor recurrence, patient age 60 years or older, subretinal fluid, cobalt isotope, anterior tumor margin posterior to equator, and worse initial visual acuity. Moderate loss of visual acuity of 5 Snellen lines or more was found in 33% at 5 years and 69% at 10 years of follow-up. From multivariable analysis, clinical factors that best predicted moderate visual acuity loss included increasing tumor thickness, worse initial visual acuity, notched plaque shape, tumor recurrence, proximity to foveola of less than 5 mm, patient age of 60 years or older, subretinal fluid, and diabetes mellitus or hypertension. When analyzing visual outcome with regard to tumor thickness, ultimate poor visual acuity of 20/200 or worse at 5 years was found in 24% with a small melanoma (≤3.0 mm), 30% with a medium melanoma (3.1-8.0 mm), and 64% with a large melanoma (>8.0 mm). When analyzing visual outcome with regard to tumor proximity to visually important structures, tumors less than 5 mm from the optic disc or foveola demonstrated poor visual acuity in 35% at 5 years, whereas those 5 mm or more from the optic disc and foveola showed poor visual acuity in 25% at 5 years. Conclusions Ultimate visual acuity after plaque radiotherapy for uveal melanoma depends on many factors, including patient age and general health, initial visual acuity, tumor location and size, subretinal fluid, radioactive isotope, and final tumor control. At 10 years' follow-up, 68% of patients demonstrate poor visual acuity. Visual acuity is most effectively preserved in eyes with small tumors outside a radius of 5 mm from the optic disc and foveola.
TL;DR: ONH images can be classified objectively and dependably by an automated procedure that does not require prior manual outlining of disc boundaries.
Abstract: PURPOSE To classify images of optic nerve head (ONH) topography obtained by scanning laser ophthalmoscopy as normal or glaucomatous without prior manual outlining of the optic disc. METHODS The shape of the ONH was modeled by a smooth two-dimensional surface with a shape described by 10 free parameters. Parameters were adjusted by least-squares fitting to give the best fit of the model to the image. These parameters, plus others derived from the image using the model as a basis, were used to discriminate between normal and abnormal images. The method was tested by applying it to ONH topography images, obtained with the Heidelberg Retina Tomograph, from 100 normal volunteers and 100 patients with glaucomatous visual field damage. RESULTS Many of the parameters derived from the fits differed significantly between normal and glaucomatous ONH images. They included the degree of surface curvature of the disc region surrounding the cup, the steepness of the cup walls, the goodness-of-fit of the model to the image in the cup region, and measures of cup width and cup depth. The statistics of the parameters were analyzed and were used to construct a classifier that gave the probability, P(G), that each image came from the glaucoma population. Images were classified as abnormal if P(G) > 0.5. The probabilities assigned to each image were in most cases close to 0 (normal) or 1 (abnormal). Eighty-seven percent of the sample was confidently classified with P(G) 0.7. Within this group, the overall classification accuracy was 92%. The overall accuracy of the method (the mean of sensitivity and specificity, which were similar) in the whole sample was 89%. CONCLUSIONS ONH images can be classified objectively and dependably by an automated procedure that does not require prior manual outlining of disc boundaries.
TL;DR: In subjects with ocular hypertension with retinal nerve fiber layer defects and normal conventional achromatic visual fields, the vertical cup-to-disc diameter ratio corrected for optic disc size, total neuroretinal rim area, rim-to -disc area ratio, and cup- to-disc area ratios corrected for disc size are the most valuable optic disc variables for early detection of glaucomatous optic nerve damage.
Abstract: PURPOSE. To describe optic disc variables assessed by evaluation of clinical optic disc photographs and to compare sensitivity and specificity of these optic disc parameters in identifying patients with ocular hypertension who have nerve fiber layer defects and normal visual fields and patients with visual field defects. METHODS. The study included 500 normal subjects, 132 patients with ocular hypertension with retinal nerve fiber layer defects and normal visual fields (preperimetric glaucoma), and 840 patients with glaucomatous visual field defects. Color stereo optic disc photographs were morphometrically evaluated. RESULTS. Highest diagnostic power for the separation between the normal group and the preperimetric glaucoma group had the vertical cup-to-disc diameter ratio corrected for its dependence on the optic disc size, total neuroretinal rim area, rim-to-disc area ratio corrected for disc size, and cup-to-disc area ratio corrected for disc size. Diagnostic power was lower for rim area in the temporal inferior and temporal superior disc sector, cup area corrected for disc size, and horizontal cup-to-disc diameter ratio corrected for disc size. Less useful for the differentiation between the normal subjects and the preperimetric glaucoma group were size of zones alpha and beta of parapapillary chorioretinal atrophy, and ratios of neuroretinal rim width and rim area comparing various optic disc sectors with each other. CONCLUSIONS. In subjects with ocular hypertension with retinal nerve fiber layer defects and normal conventional achromatic visual fields, the vertical cup-to-disc diameter ratio corrected for optic disc size, total neuroretinal rim area, rim-to-disc area ratio, and cup-to-disc area ratio corrected for disc size are the most valuable optic disc variables for early detection of glaucomatous optic nerve damage. Correction for optic disc size is necessary for optic disc variables directly or indirectly derived from the optic cup. Parapapillary atrophy is less important in the early detection of glaucoma. (Invest Ophthalmol Vis Sci. 2000;41:1764 ‐1773)
TL;DR: In this article, the ability of expert clinicians, using qualitative assessment of stereoscopic optic disc photographs, and confocal scanning laser ophthalmoscope imaging to discriminate between healthy persons and patients with early glaucoma was compared.
TL;DR: In this article, the pupil of the eye is projected through the pupil onto the fundus and the reflected image from the retina is used to measure non-photo-reactive blood components such as hemoglobin or bilirubin.
Abstract: Illuminating light (12) of selected wavelengths in the visible or infrared range is projected through the pupil of the eye (10) onto the fundus. The light reflected back, out through the pupil is detected (22), and analyzed, preferably using the area of the optic disk for analyzing the retinal vessels overlying the optic disk. Specific wavelengths of illuminating light may be chosen for each blood component to be analyzed depending on the spectral characteristics of the substance being analyzed. The reflected image from the retina may be used to measure non-photo-reactive blood components such as hemoglobin, and photo-reactive components such as bilirubin. For the measurement of photo-reactive components, images may be taken before, and after, or during, illumination of the eye with light at wavelengths which will affect the photo-reactive analyte, enabling measurements of the concentration of the analyte.
TL;DR: Reduced optic disk perfusion in patients with open-angle glaucoma is evidenced from two independent methods in the present study and indicates that reduced ocular blood flow in these patients is linked to visual field changes.
TL;DR: In this paper, the pupil of the eye is projected through the pupil onto the fundus, and the light reflected back and out through pupil is detected and analyzed, preferably using the area of the optic disk for analyzing the retinal vessels overlying the optic disks.
Abstract: Illuminating light of selected wavelengths in the visible or infrared range is projected through the pupil of the eye onto the fundus, and the light reflected back and out through the pupil is detected and analyzed, preferably using the area of the optic disk for analyzing the retinal vessels overlying the optic disk. Specific wavelengths of illuminating light may be chosen for each blood component to be analyzed depending on the spectral characteristics of the substance being analyzed. The reflected image from the retina may be used to measure non-photoreactive blood components such as hemoglobin, and photoreactive components such as bilirubin. For the measurement of photoreactive components, images may be taken before and after, or during, illumination of the eye with light at wavelengths which will affect the photoreactive analyte, enabling measurements of the concentration of the analyte.
TL;DR: Spatial properties of the DLS matched those of the posterior vitreous face in the situations examined, and it was concluded that anteronasal papillofoveal traction may generate some macular holes.
Abstract: Objectives To determine the validity of the assumption that optical coherence tomographic scans of macular holes have a discrete linear signal (DLS) that represents a detached posterior vitreous face, and to analyze the DLS in macular hole pathogenesis. Methods Optical coherence tomographic scans were taken of 3 situations in which the vitreous conditions were known: (1) dissected intact vitreous, (2) clinically evident Weiss rings, and (3) maculae before and after saccades in eyes without a biomicroscopic posterior vitreous detachment. In addition, 70 eyes of 35 patients with macular holes underwent clinical examination and optical coherence tomographic scanning that passed through the optic disc and the fovea or macular hole. Results Spatial properties of the DLS matched those of the posterior vitreous face in the situations examined. Of the 70 eyes, 16 (23%) had a biomicroscopic posterior vitreous detachment, whereas a DLS was demonstrated in 40 (57%). Of the 54 eyes without a biomicroscopic posterior vitreous detachment, 18 (33%) had a DLS attached focally to the optic disc margin and the fovea or macular hole. All 7 of the "can opener" holes examined had a nasally "hinged" central flap, 6 with a focally attached DLS. Conclusions The DLS corresponds to the posterior vitreous face. Anteronasal papillofoveal traction may generate some macular holes.
TL;DR: The development of an automatic fundus image processing and analytic system to facilitate diagnosis of the ophthalmologists is described and the results seem promising and useful to clinical work.
Abstract: Diabetic retinopathy is the leading cause of the blindness in the working age population. If the disease is detected early and treated promptly, much of the visual loss can be prevented. This paper describes the development of an automatic fundus image processing and analytic system to facilitate diagnosis of the ophthalmologists. The algorithms to detect the optic disk, blood vessels and exudates are investigated. The optic disk is identified by the method of Sobel edge detector and LSR in the candidate area. The blood vessels and the exudates are extracted by Kirsch's method in the different color components of the color fundus image. The processing results of the proposed methods are also presented. More than thirty fundus images have been tested and the results of the system seem promising and useful to clinical work.
TL;DR: Change in a subset of ocular hypertensive patients which could predate the development of glaucomatous visual field loss is identified, suggesting the HRT could be of value in the sequential follow up of those suspected of havingglaucoma by identifying eyes at risk of developing glAUcoma.
Abstract: AIM—To determine if global and segmental changes in optic disc parameters of sequential Heidelberg retina tomograph (HRT) images develop in individual ocular hypertensive (OHT) patients without white on white visual field defects.
METHODS—Patients and normal controls were recruited from a prospective ocular hypertension treatment trial. The subject groups consisted of 21 OHT patients who had converted to early glaucoma on the basis of visual field criteria (24-2 program on the Humphrey perimeter), 164 OHT subjects with normal visual fields, and 21 normal controls. Sequential HRT images 16-21 months apart were obtained for each subject and segmental optic disc parameters were measured to determine if any change had occurred. From the analysis of sequential HRT images of the 21 normal eyes we established normal limits of interimage variation. Individual discs in each group showing changes above the 95% limit of normal variability were then sought.
RESULTS—Several segmental and global optic disc parameters were found to show significant change in the converter group before confirmed visual field change, confirming our previously published results. Individual optic disc analysis using the 95% limit of normal variability data demonstrated glaucomatous change in 13 out of 21 converter eyes. 47 of the 164 OHT eyes with normal visual fields showed change in global and segmental parameters in a "glaucomatous" direction above the level expected for normal variability. The parameters which changed most frequently in the OHT eyes were: global cup volume (6.7% of discs), inferonasal cup volume (11%), inferotemporal cup volume (8.5%), and superotemporal cup area (7.3%).
CONCLUSIONS—We have identified change in a subset of ocular hypertensive patients which could predate the development of glaucomatous visual field loss. The HRT could be of value in the sequential follow up of those suspected of having glaucoma by identifying eyes at risk of developing glaucoma. However, further refinement of the technique is required to eliminate some of the inherent variability of the analysis method described, and to increase the ability to detect at risk individuals.
TL;DR: The characteristic clinical features of optic disc metastasis should help differentiate it from other causes of swollen optic disc and patient prognosis is poor.
Abstract: Background Little information is available on metastatic tumors to the optic disc. Objective To determine the clinical features and prognosis of patients with optic disc metastasis. Design Retrospective chart review. Results Of 660 consecutively evaluated patients with intraocular metastasis, 30 (4.5%) (31 eyes) had metastatic cancer to the optic disc; 24 (80%) were women and 6 (20%) were men. Mean age at the time of ocular diagnosis was 55 years. The primary neoplasm was in the breast in 13 patients (43%), in the lung in 8 (27%), in the intestine in 1 (3%), in the kidney in 1 (3%), and in the prostate in 1 (3%); the primary neoplasm was never determined in 6 patients (20%). The optic disc metastasis was unilateral in 29 patients (97%) and bilateral in 1 (3%). Ophthalmoscopically, the disc metastasis appeared as a diffuse enlargement of the optic disc in 26 eyes (84%) and as a distinct nodule in 5 (16%). There was an adjacent juxtapapillary choroidal component to the metastatic disc lesion in 23 eyes (74%), and the optic disc was involved without a retinal or choroidal component in 8 (26%). Other associated findings included some degree of secondary disc edema in all eyes, buried disc blood vessels in 23 (74%), and splinter hemorrhages in 13 (42%). Fine needle aspiration biopsy was useful in establishing the diagnosis in all 5 eyes in which it was performed. Mean survival was 13 months after diagnosis of the disc metastasis. Conclusions Metastasis to the optic disc accounts for 5% of all intraocular metastases. It can occur as invasion from a juxtapapillary choroidal metastasis or as isolated optic disc metastasis. Breast and lung cancers are the most common primary neoplasms that account for metastasis to the optic disc. The primary site is never determined in 20% of patients. The characteristic clinical features of optic disc metastasis should help differentiate it from other causes of swollen optic disc. Patient prognosis is poor.
TL;DR: The present survey indicates that RGC growth cones are guided by many molecular cues along their pathway which are recognized by receptors on their surface, which convert the growth encouraging signal into a repulsive one which drives growth cones into the nerve.
TL;DR: Results indicate that NO is continuously released in human choroidal and ONH vessels.
Abstract: PURPOSE There is evidence from animal studies that nitric oxide (NO) is a major determinant of ocular blood flow. In humans NO synthase inhibition reduces pulsatile choroidal blood flow, but no data on optic nerve head (ONH) vasculature are available yet. The goal of this study was to investigate the effects of NO synthase inhibition on human choroidal and ONH blood flow using laser Doppler flowmetry. METHODS The study design was a randomized, placebo-controlled, double-masked, balanced three-way crossover. On separate study days 12 healthy male subjects received infusions of N:(G)-nitro-L-arginine (L-NMMA; either 3 mg/kg over 5 minutes followed by 30 microg/kg per minute over 55 minutes or 6 mg/kg over 5 minutes followed by 60 microg/kg per minute over 55 minutes) or placebo. The effects of L-NMMA or placebo on choroidal and ONH blood flow were measured with laser Doppler flowmetry. In addition, laser interferometric measurement of fundus pulsation was performed in the macula to assess pulsatile choroidal blood flow. RESULTS L-NMMA reduced all outcome parameters in the choroid and the ONH. The higher dose of L-NMMA caused a significant decrease in blood flow in the choroid (-26% +/- 9%; P: < 0.001) and the ONH (-20% +/- 16%; P: < 0.001) as evidenced from laser Doppler flowmetry and a significant decrease in fundus pulsation amplitude (-26% +/- 5%; P: < 0.001). CONCLUSIONS These results indicate that NO is continuously released in human choroidal and ONH vessels.
TL;DR: Tele-ophthalmic consultations were conducted between a hospital in East Java, Indonesia, and an ophthalmology centre in Perth, Western Australia, and the images received were considered to be of excellent quality and readily interpreted by ophthalmologists in terms of the likely presence of glaucoma.
Abstract: Tele-ophthalmic consultations were conducted between a hospital in East Java, Indonesia, and an ophthalmology centre in Perth, Western Australia. Twenty-two eyes of 14 subjects were screened for glaucoma using a hand-held fundus camera. Optic disc images comprised 267 x 234 pixels at 24 bit/pixel (187 kByte). The images were compressed and stored together with patient information on a laptop computer. The images were then transmitted to Perth using either a mobile phone or a satellite phone, taking 170 s or 240 s, respectively. Images were also compressed to five different compression levels before transmission. At a compression ratio of 1:5, the images were 36 kByte in size and took 29 s to transmit by mobile phone and 60 s by satellite phone. To measure the loss of quality, the root mean square error was calculated for each colour component, comparing the transmitted and original images. The coefficients of variation were 10% (green), 15% (blue) and 22% (red). The images received in Perth were considered to be of excellent quality and readily interpreted by ophthalmologists in terms of the likely presence of glaucoma.
TL;DR: Uveitic neovascularization appears to be determined most directly by the severity of the inflammation and the presence of retinal nonperfusion, and should only be considered when corticosteroids and focal photocoagulation are ineffective or are otherwise contraindicated.
Abstract: Neovascularization is an infrequent but serious complication of uveitis The retina and optic disk appear to be affected most often, although new blood vessels may arise from the iris, ciliary body, and choroid as well Although neovascularization can usually be identified on careful clinical examination, some patients may require fluorescein angiography or UBM Numerous neovascular growth and inhibitory factors have been identified experimentally Clinically, however, uveitic neovascularization appears to be determined most directly by the severity of the inflammation and the presence of retinal nonperfusion Virtually all patients with uveitic neovascularization deserve a trial of local or systemic corticosteroids Laser photocoagulation can be considered in those patients who fail to respond to corticosteroid therapy, but only when retinal nonperfusion has been demonstrated on fluorescein angiography Surgical excision of newly formed vessels is reserved for selected patients with CNV and uveitis, but should only be considered when corticosteroids and focal photocoagulation are ineffective or are otherwise contraindicated
TL;DR: The results suggest that, in some patients, moderate decreases in intraocular pressure may affect disk topography, as measured by Heidelberg Retina Tomograph.
TL;DR: Compared with standard perimetry, SWAP may improve the detection of progressive glaucoma and identify more patients than standardPerimetry as having progressive glaunching changes of the optic disc.
Abstract: Objective To compare progression in short-wavelength automated perimetry (SWAP) and white-on-white (standard) perimetry in eyes with progressive glaucomatous changes of the optic disc detected by serial stereophotographs. Methods Forty-seven glaucoma patients with at least 2 disc stereophotographs more than 2 years apart, along with standard perimetry and SWAP examinations within 6 months of each disc photo of the same eye, were included in the study. The mean follow-up time was 4.1 years (range, 2.0-8.9 years). Baseline and follow-up stereophotographs were then graded and compared for the presence of progression. Progression in standard perimetry and SWAP, using the Advanced Glaucoma Intervention Study scoring system and a clinical scoring system, was compared between eyes with progressive change on stereophotographs and those without. Results Twenty-two of 47 eyes showed progressive change by stereophotographs. There was a statistically significant difference in the mean change in Advanced Glaucoma Intervention Study scores for both standard perimetry ( P P P = .04). Conclusions Short-wavelength automated perimetry identified more patients than standard perimetry as having progressive glaucomatous changes of the optic disc. Compared with standard perimetry, SWAP may improve the detection of progressive glaucoma.
TL;DR: The results indicated the probable association of a decrease in retinal, choroidal and optic disk blood flow in the inferior and nasal quadrant with visual field loss in the superior quadrant and an increasing blood flow for enlargement of pallor.
Abstract: Computerized image analysis, including fluorescein angiography, was used to evaluate the retinal, choroidal and optic disk blood flow in 16 patients with normal-tension glaucoma (NTG) and to correlate this measurement with visual fields, retinal vessel width, optic disk pallor and blood pressure (BP). The angle of the ascending slope of the fluorescein dye curve was measured as an index of blood flow from the densitometric and time curves of the fluorescein angiograms in the optic disk, peripapillary choroid, retinal artery and vein for each quadrant. While the ascending slope as well as the retinal vessel width were most reduced in the inferior and nasal regions, the mean threshold was lowest in the superior and nasal quadrants. There were positive significant correlations between artery width and threshold value, between angles of slopes and pallor. In addition, systolic BP had a negative correlation with pallor, and diastolic BP had a positive one with slope in the choroid. These results indicated the probable association of a decrease in retinal, choroidal and optic disk blood flow in the inferior and nasal quadrants as well as vessel width in the inferior nasal quadrant with visual field loss in the superior quadrant, and also demonstrated an increasing blood flow for enlargement of pallor. A decrease in BP was found to be related to reduced blood flow in choroid and optic disk impairment.
TL;DR: Combining quantitative optic disc variables by discriminant analysis functions, the predictive power of semiautomatic quantitative optic nerve head evaluation can be improved by providing the ophthalmologist with a diagnostic score for the detection of glaucomatous optic nerve damage.
Abstract: AIM—To evaluate and compare four different mathematical formulas for the early detection of morphometric optic nerve head changes in chronic open angle glaucoma.
METHODS—The optic nerve heads of 161 patients with perimetrically defined glaucomatous optic nerve damage and of 194 normal subjects were examined by confocal laser scanning tomography. Using four formulas of linear discriminant analysis and the optic cup shape measure as the single optic disc variable, the predictive power of each of these methods was examined to differentiate between the normal eyes and the glaucoma eyes.
RESULTS—The highest predictive power had an optic disc sector based formula, in particular in eyes with medium and large optic discs. This optic disc sector based formula was the one with the best agreement with the other formulas examined. It achieved a better predictability than any single optic disc variable evaluated.
CONCLUSIONS—Combining quantitative optic disc variables by discriminant analysis functions, the predictive power of semiautomatic quantitative optic nerve head evaluation can be improved by providing the ophthalmologist with a diagnostic score for the detection of glaucomatous optic nerve damage. Because of the pattern of glaucomatous neuroretinal rim loss, an optic disc sector based discriminant formula may have a higher diagnostic precision than other formulas in detecting early glaucomatous damage.
TL;DR: It appears that the naso-temporal asymmetries of the oscillation-rich components are produced primarily by the relative alignment and enhancement of RC and ONHC wavelets in the temporal retina, and misalignment and partial cancellation in the nasal retina.
Abstract: This study examines the characteristics and the naso-temporal asymmetries of the higher-order oscillatory components of the multifocal electroretinogram (mERG). The magnitude of the mERG asymmetry and the mechanisms which produce it have not been studied previously. We recorded the mERG from seven normal observers using slow multifocal flicker and response filtering of 10-300 Hz. This permitted, without additional filtering, examination of the dominant first order component and the oscillation-rich components in the first and second order kernels. The oscillatory components in the two kernels had multiple peaks separated by about 6.8 ms, similar to those of conventional oscillatory potentials. Naso-temporal asymmetry of the three response components was analyzed in three groups (concentric rings around the fovea) spanning 1.5-10 deg of retinal eccentricity. The oscillation-rich components were, on average, approximately 14% larger in amplitude in the temporal retina than in corresponding nasal locations (p < 0.05) while the dominant first order component was not asymmetrically distributed. We tested the hypothesis that the asymmetry could be modeled as a combination of a retinal component (RC) and an optic nerve head component (ONHC) which varies in latency as a function of distance from the optic disc. We found that both oscillatory components and the dominant first order response could be decomposed into RCs and ONHCs that are symmetrically distributed. Thus, it appears that the naso-temporal asymmetries of the oscillation-rich components are produced primarily by the relative alignment and enhancement of RC and ONHC wavelets in the temporal retina, and misalignment and partial cancellation in the nasal retina.
TL;DR: The thickness of total as well as superior and inferior quadrant peripapillary RNFL as measured by scanning laser polarimetry and tomography increased significantly with an increase in optic disc size and the total cross sectional area occupied by RNFL decreased significantly with a increase in age.
Abstract: Aims—To evaluate the relation of the optic nerve head topographic measurements and age with the thickness of the retinal nerve fibre layer (RNFL) in normal Caucasoid subjects by means of scanning laser polarimetry and tomography. Methods—Topographic optic disc measurements and RNFL thickness values of 38 normal Caucasoid subjects of both sexes aged 20 to 78 were measured using a confocal scanning laser ophthalmoscope and a confocal scanning laser polarimeter. One eye was randomly selected for statistical analysis.The eVects of optic disc size, age, and optic disc head topographic measurements of total and regional RNFL thickness were evaluated. Results—Age showed a significant correlation with the integral of the total RNFL thickness (R=˛0.341, p 0.05). Conclusion—The thickness of total as well as superior and inferior quadrant peripapillary RNFL as measured by scanning laser polarimetry increased significantly with an increase in optic disc size. The cross sectional area occupied by superior and inferior polar RNFL increased significantly with an increase in NRA. The total cross sectional area occupied by RNFL decreased significantly with an increase in age. The eVects of optic disc size, age, and NRA should be considered when the peripapillary RNFL thickness is evaluated. (Br J Ophthalmol 2000;84:473‐478)