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The article presents the case of a 40-year-old white woman who sought care for a history of decreased vision in her right eye. The optic nerve of the right eye of the patient was normal in size and color and contained a small slit-like cup. Optic nerve pits and typical colobomas are probably embryologically distinct congenital excavations of the optic nerve.

Objective To investigate differences in visual function, optic disc topography, and retinal nerve fiber layer (RNFL) thickness between healthy eyes of blacks and whites. Methods Visual function was assessed in healthy eyes of 50 blacks and 50 whites using standard automated perimetry, short-wavelength automated perimetry, and frequency doubling technology perimetry. Optic disc topography and RNFL thickness were measured using the Heidelberg Retina Tomograph and the optical coherence tomograph. Results Mean standard automated perimetry mean deviations were within the normal range for both groups. Blacks had worse mean deviation values than whites using frequency doubling technology perimetry (mean ± SD, -1.8 ± 3.2 dB vs -0.1 ± 2.4 dB), blacks had larger optic disc areas than whites using the Heidelberg Retina Tomograph (mean ± SD, 2.1 ± 0.4 mm2 vs 1.7 ± 0.4 mm2), the RNFL of blacks was thicker than that of whites by 16.91 μm superiorly and 10.10 μm inferiorly using optical coherence tomography, and blacks had slightly higher intraocular pressures than whites (mean ± SD, 16.5 ± 2.5 mm Hg vs 15.2 ± 3.2 mm Hg) and thinner central corneas (mean ± SD, 540.5 ± 43.2 μm vs 560.9 ± 35.5 μm). No racial differences were found in mean RNFL thickness, pattern standard deviation on all tests, or any of the short-wavelength automated perimetry variables. Conclusions Minimal racial differences in visual function were found, but race significantly affected optic disc topography and superior and inferior RNFL thickness measurements in healthy eyes. The racial differences observed for intraocular pressure could theoretically increase after correcting for central corneal thickness. Prospective studies are needed to further investigate these findings. [ABSTRACT FROM AUTHOR]

Background The ocular fetal vasculature normally regresses by apoptosis but for unknown reasons fails to regress in the human disease persistent fetal vasculature. Objective To investigate whether proapoptotic Bcl-2 members, Bax and Bak, are involved in fetal vasculature regression. Methods Adult eyes from mice deficient in Bax and/or Bak were examined grossly and histologically for persistence of fetal vasculature. Vessels were identified by the presence of lumens and erythrocytes and by Factor VIII labeling. Eyes from postnatal day 7 mice were processed for terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate nick-end labeling (TUNEL) analysis to determine if deficiency of Bax and Bak results in defective developmental apoptosis. Results Only bax-/-bak-/- eyes retained fetal vasculature into adulthood. This vasculature consisted of a hyaloid artery emerging from the optic nerve head and intravitreal and perilental vessels but not a pupillary membrane. At postnatal day 7, wild-type but not bax-/-bak-/- eyes had TUNEL-positive cells in the fetal vasculature. Conclusions These data demonstrate that Bax and Bak serve overlapping functions in fetal vasculature regression, emphasizing the importance of apoptosis in developmental remodeling. Clinical Relevance Disruption of Bax and Bak results in persistent fetal vasculature in knockout mice, providing a model of the human disease persistent fetal vasculature to investigate its etiology and potential therapies. [ABSTRACT FROM AUTHOR]

Objective To evaluate the risk of peripheral anterior synechiae (PAS) and glaucomatous optic neuropathy attributable to primary angle closure at varying anterior chamber depths (ACDs) in two East Asian populations. Methods Participants 40 years and older were from 2 population-based glaucoma surveys in Mongolia and Singapore. Central ACD was measured by optical pachymetry. Presence of PAS was determined by dynamic gonioscopy. Cases with secondary PAS were excluded. Glaucomatous optic neuropathy was diagnosed in subjects with structural and functional evidence of glaucoma. Results A total of 2032 subjects, consisting of 942 Mongolians and 1090 Chinese Singaporeans, were included in this study. A logistic model of the relationship between ACD and PAS among Singaporeans showed a consistent, incremental increase in PAS across the entire range of ACD. In deeper anterior chambers the rate of PAS exceeded that seen in Mongolians. In Mongolians, there was a clear threshold for ACD (2.4 mm) at or above which PAS were very uncommon. With ACD less than 2.4 mm, the rate of PAS rose rapidly to overtake that seen in Singaporeans. Conclusions Shallow anterior chambers are a significant risk factor for angle closure in East Asians, although the nature of the association is specific to the individual population. There was a trend toward higher rates of glaucomatous optic neuropathy in people with the shallowest anterior chambers. [ABSTRACT FROM AUTHOR]

Reports on the case of cavernous hemangioma of the retina. Location of the lesion in the posterior pole or optic nerve head; Symptoms observed in patients; Measurement of the patient's visual acuity to identify abnormalities in the retinal veins.

Investigates the occurrence of gaucher disease. Safety and efficacy of enzyme replacement therapy with intravenous infusions of glycosylceramidase for the treatment of the visceral manifestations of Gaucher disease; Presentation of the case of woman with corrected visual acuities; Characterization of the diseases.

Objective: To develop a method for comparing multifocal visual-evoked potential (mfVEP) responses and behaviorally determined visual fields with structural measures of the optic nerve head. Methods: Humphrey 24-2 visual fields and mfVEPs were obtained from each eye of 20 patients with open-angle glaucoma. Monocular and interocular analyses were performed to identify locations with abnormal mfVEP responses. Optic discs were assessed with a confocal scanning laser ophthalmoscope (Heidelberg Retina Tomograph II). The image of the optic nerve head was divided into 6 sectors. The rim and disc area measurements for each sector were compared with those in a normal database using Moorfields regression analysis. The optic nerve head measurements for the 6 sectors were related to the Humphrey visual field locations and the 60 sectors of the mfVEP display. Results: Of 240 sectors tested (40 eyes × 6 sectors), 18.8% on Humphrey visual field, 22.1% on mfVEP, and 10.8% on confocal scanning laser ophthalmoscopic testing were significantly different from those of control subjects. There were no significant deficits in 165 sectors. There was agreement for 86.7% of the sectors when the Humphrey visual field and mfVEP results were compared. The confocal scanning laser ophthalmoscopic results were in agreement for 84.6% of these sectors. Conclusions: The method used allows for a comparison among measures of visual function and a structural measure of the optic nerve head. In general, the results of the functional and structural measures showed agreement; however, there were clear examples of disagreements that merit further study. [ABSTRACT FROM AUTHOR]

Objective: To examine tissue hypoxia in the retina and optic nerve head of glaucomatous eyes by the assessment of a transcription factor, hypoxia-inducible factor 1α (HIF-1α), which is tightly regulated by the cellular oxygen concentration. Methods: Using immunohistochemical analysis, the cellular localization of HIF-1α was studied in the retina and optic nerve head of 28 human donor eyes with glaucoma compared with 20 control eyes from healthy donors matched for several characteristics. The relationship between the retinal regions that exhibited immunostaining for HIF-1α and functional damage was examined using visual field data. Results: There was an increase in the immunostaining for HIF-1α in the retina and optic nerve head of glaucomatous donor eyes compared with the control eyes. In addition, the retinal location of the increased immunostaining for HIF-1α in some of the glaucomatous eyes was closely concordant with the location of visual field defects recorded in these eyes. Conclusions: Because the regions of HIF-1α induction represent the areas of decreased oxygen delivery and hypoxic stress, information obtained from this study provides direct evidence that tissue hypoxia is present in the retina and optic nerve head of glaucomatous eyes, and hypoxic signaling is a likely component of the pathogenic mechanisms of glaucomatous neurodegeneration. Clinical Relevance: These findings support the presence of tissue hypoxia in the retina and optic nerve head of glaucomatous patients. [ABSTRACT FROM AUTHOR]

Objective Bornholm eye disease (BED) consists of X-linked high myopia, high cylinder, optic nerve hypoplasia, reduced electroretinographic flicker with abnormal photopic responses, and deuteranopia. The disease maps to chromosome Xq28 and is the first designated high-grade myopia locus (MYP1). We studied a second family from Minnesota with a similar X-linked phenotype, also of Danish descent. All affected males had protanopia instead of deuteranopia. Methods X chromosome genotyping, fine-point mapping, and haplotype analysis of the DNA from 22 Minnesota family individuals (8 affected males and 5 carrier females) and 6 members of the original family with BED were performed. Haplotype comparisons and mutation screening of the red-green cone pigment gene array were performed on DNA from both kindreds. Results Significant maximum logarithm of odds scores of 3.38 and 3.11 at θ = 0.0 were obtained with polymorphic microsatellite markers DXS8106 and DXYS154, respectively, in the Minnesota family. Haplotype analysis defined an interval of 34.4 cM at chromosome Xq27.3-Xq28. Affected males had a red-green pigment hybrid gene consistent with protanopia. We genotyped Xq27-28 polymorphic markers of the family with BED, and narrowed the critical interval to 6.8 cM. The haplotypes of the affected individuals were different from those of the Minnesota pedigree. Bornholm eye disease–affected individuals showed the presence of a green-red hybrid gene consistent with deuteranopia. Conclusions Because of the close geographic origin of the 2 families, we expected affected individuals to have the same haplotype in the vicinity of the same mutation. Mapping studies, however, suggested independent mutations of the same gene. The red-green and green-red hybrid genes are common X-linked color vision defects, and thus are unrelated to the high myopia and other eye abnormalities in these 2 families. Clinical Relevance X-linked high myopia with possible cone dysfunction has been mapped to chromosome Xq28 with intervals of 34.4 and 6.8 centimorgan for 2 families of Danish origin. [ABSTRACT FROM AUTHOR]

Objective: To determine how the photopic negative response (PhNR) is altered in patients with optic nerve atrophy. Methods: Ten patients with optic nerve atrophy induced by compression, trauma, or inflammation were examined. There were 6 men and 4 women with a mean age of 52.4 years. Ten age-matched control subjects were examined with the same protocol. Full-field electroretinograms were recorded, and the retinal nerve fiber layer thickness surrounding the optic nerve head was measured by means of optical coherence tomography. Results: The amplitudes of the rod, maximum, cone, and 30-Hz flicker electroretinograms of the affected eyes were not different from those of the corresponding waves of the contralateral unaffected eyes or control eyes. In contrast, the amplitude of the PhNR was significantly smaller in the affected eyes than in the contralateral (P = .005) or control (P<.001) eyes. The decrease in amplitude of the PhNR preceded thinning of the retinal nerve fiber layer. There was a significant correlation between the PhNR amplitude and retinal nerve fiber layer thickness in eyes with optic nerve atrophy (r = 0.879; P<.001). Conclusions: Selective reduction and loss of the PhNR amplitude was found in eyes with optic nerve atrophy, which suggests that the PhNR can be used to evaluate the function of ganglion cells or their axons. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate absolute filling defects of the optic nerve head in normal tension glaucoma (NTG) and primary open-angle glaucoma (POAG) and to compare the filling defects with topographic analysis of the optic disc. Methods: Twenty-five patients with NTG, 25 patients with POAG, and 25 age-matched controls were included. Fluorescein angiograms were performed by means of a scanning laser ophthalmoscope. The extent of absolute filling defects of the optic nerve head was assessed using digital image analysis of early-phase angiograms. Topographic measurements of the optic disc were acquired using the Heidelberg Retina Tomograph II. Results: Absolute filling defects were significantly larger (P = .001) and were seen more often (P<.001) in patients with NTG (n = 18) and POAG (n = 19) compared with controls (n = 3). Rim area (P = .006), rim volume (P = .007), cup-disc area ratio (P = .008), linear cup-disc ratio (P = .005), maximum cup depth (P = .002), cup shape measure (P = .03), and nerve fiber layer thickness (P = .008) and cross-sectional area (P = .006) were significantly different between patients with glaucoma and controls. Absolute filling defects were significantly correlated with cup area (r = 0.31; P = .007), rim area (r = -0.38; P<.001), rim volume (r = -0.35; P = .002), cup-disc area ratio (r = 0.49; P<.001), linear cup-disc ratio (r = 0.48; P<.001), cup shape measure (r = 0.27; P = .02), and nerve fiber layer thickness (r = -0.33; P = .004) and cross-sectional area (r = -0.30; P = .009). Conclusions: Fluorescein filling defects of the optic disc are present in NTG and POAG. The extent of these filling defects is correlated with the morphologic disc damage. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effect of intraocular pressure (IOP) reduction on long-term progression or stability in patients with exfoliation glaucoma. Design: Multicenter (Greece, Spain, Russia, and Hungary), retrospective analysis. Methods: Medical record analysis of 167 patients with at least 5 years of follow-up, who were stable (n = 85) or whose condition had progressed (n = 82) after the beginning of the follow-up period. Results: The mean ± SD IOP was 18.1 ± 2.6 mm Hg in the stable group and 20.1 ± 4.3 mm Hg in the progressed group (P<.001). The mean ± SD follow-up time was 6.1 ± 2.3 years for the stable group and 3.4 ± 1.7 years for the progressed group. The mean SD for each patient's average IOP was 2.9 mm Hg for the stable group and 4.6 mm Hg for the progressed group (P<.001). Twenty-eight percent of patients who had a mean IOP of 17 mm Hg or lower, 43% of those with an IOP of 18 to 19 mm Hg, and 70% of those with an IOP of 20 mm Hg or higher progressed. Progressed patients had statistically greater optic disc damage at baseline and more medication changes and trabeculectomies during follow-up than stable patients (P<.05). Conclusion: This study suggests that IOP reduction helps to prevent glaucoma progression in patients with exfoliation glaucoma, although it does not guarantee the prevention or worsening of the disease. [ABSTRACT FROM AUTHOR]

Aggressive primary orbital melanoma in a 40 year old man with no predisposing ocular features is studied. A computed tomographic scan of the orbits revealed a well-defined intraconal mass that was discrete from the optic nerve and the horizontal rectus muscles. In the following 6 weeks, the proptosis enlarged, progressing from 3 mm to 8mm. There was conjunctival exposure with ulceralation, marked global restriction of movement, and transient visual obscurations. A lateral orbitotomy with excision biopsy was performed and large pigmented mass was removed, histological analysis of which showed the lesion to he an orbital melanoma.

Objective: To quantify an apparent nasotemporal asymmetry in the location of retinopathy of prematurity with respect to the optic disc. Methods: Twenty-four–bit color images were captured using a contact digital fundus camera during routine screening. Semiautomated measurements were undertaken to determine the distance between the optic disc and retinopathy located in the nasal and temporal regions of the retina. Results: Forty-nine image pairs (17 right eye, 32 left eye) were captured from 10 infants during a period of 32 to 40 weeks postmenstrual age. For right eyes, averaged across age, the mean (SD) distance between the optic disc and temporal retinopathy was 426 (26) pixels and that between the optic disc and nasal retinopathy was 330 (26) pixels. Corresponding measurements for the left eye were 428 (30) and 332 (24) pixels. This observed asymmetry was found to be statistically significant in both left and right eyes (Mann-Whitney U test, P<.01). While the distance between the optic disc and retinopathy increased with age by 10 to 17 pixels per week, the extent of the asymmetry did not vary systematically with age. Conclusion: The location of retinopathy of prematurity is asymmetric along the horizontal meridian with respect to the optic disc—an observation germane to retinal vascular development, the pathogenesis of retinopathy of prematurity, and current disease classification by circular (symmetric) zones. [ABSTRACT FROM AUTHOR]

Objective: To evaluate a new Fourier-based analysis method for diagnosing glaucoma using retinal nerve fiber layer (RNFL) thickness estimates obtained from the optical coherence tomograph (OCT) (OCT 2000) and the scanning laser polarimeter (GDx). Methods: We obtained RNFL thickness estimates from 1 eye of 38 healthy individuals and 42 patients with early glaucomatous visual field loss using the OCT and GDx devices. The shape of the RNFL double-hump pattern was assessed using Fourier analysis, and values were entered into a linear discriminant analysis. Receiver operating characteristic (ROC) curves were used to compare the performance of the Fourier-based metrics against other commonly used RNFL analytical procedures. Reliability was assessed on independent samples by the split-half method. Correlations were calculated to determine the extent to which the Fourier discriminant measures and other RNFL measures covaried between the 2 devices and the relationship between these RNFL measures and visual field measures. Results: Sensitivity and specificity for the linear discriminant function (LDF) based on the Fourier analysis of the OCT data were 76% and 90%, respectively, and the area under the ROC curve was 0.925 (SEM, 0.028). For the GDx data, the Fourier-based LDF yielded sensitivity and specificity of 82% and 90%, respectively, with an ROC curve area of 0.928 (SEM, 0.029). These values were better than those determined using the GDx number, a previous discriminant function using GDx variables and OCT thickness values. The Fourier-based LDFs and numerous other measures were significantly correlated between the 2 devices. For each device, the visual field measures correlated most highly with the Fourier-based LDF measure. Conclusions: For both devices, the LDF based on the output from a Fourier analysis of RNFL data resulted in better diagnostic capability compared with other common RNFL analytical procedures. That this technique improves RNFL analysis is also supported by the better correlations between visual field measures and the Fourier-based LDF measures. [ABSTRACT FROM AUTHOR]

Objective: To determine if scanning laser polarimetry (SLP) measures form birefringence of the retinal nerve fiber layer (RNFL). Methods: Consecutive patients with either acute unilateral disc edema or chronic diffuse unilateral disc atrophy underwent SLP using the GDx Nerve Fiber Analyzer (Laser Diagnostic Technologies Inc, San Diego, Calif). The former group had peripapillary RNFL edema, presumably with no change in form birefringence elements, while the latter had optic nerve atrophy, presumably with a loss of birefringence elements in the RNFL. A subset of patients with acute unilateral disc edema who subsequently developed disc atrophy had repeated SLP at 6 months. Intereye and intertest comparisons of 6 SLP parameters representative of RNFL thickness were performed using the paired t test. Results: In the acute unilateral disc edema group (n=28), none of the SLP parameters were significantly increased in affected vs fellow eyes. In the chronic unilateral disc atrophy group (n=30), all SLP parameters were significantly decreased in affected vs fellow eyes (P<.001). Patients with disc edema who had a follow-up SLP demonstrated significant declines of all parameters in the affected eyes (P<.007) but no change in SLP parameters in unaffected eyes. Conclusion: Scanning laser polarimetry measures form birefringence properties of the RNFL, but not necessarily the RNFL thickness. [ABSTRACT FROM AUTHOR]

Objective: It has been shown recently that the application of indocyanine green (ICG) over the retinal surface is followed by prolonged staining of the optic disc. This study was performed to analyze the diffusion of ICG in the optic tract. Methods: Anterograde diffusion of ICG was evaluated after injection into the vitreous of rabbits. Retrograde diffusion was evaluated after microinjection into the lateral geniculate nucleus of rats. Results: Anterograde and retrograde diffusion occurred along the axons at a rate of about 2 mm per hour when ICG was injected. Anterograde staining of the visual pathway persisted for several weeks. After injection into the lateral geniculate nucleus, fluorescent retinal ganglion cells could be visualized for at least 7 days in conscious rats by conventional infrared photography. Microscopic examination findings of retrograde-labeled retinas showed the presence of ICG vesicles inside the axons, cytoplasm, and dendrites of retinal ganglion cells. No evidence of toxic effects was detected by optical microscopy. Conclusions: Indocyanine green is a fast bidirectional axonal tracer. Injection into normal vitreous results in long-term staining of the visual pathway. In vivo counting of ICG-labeled retinal ganglion cells in rats can be performed for several days after injection. Indocyanine green is therefore potentially of interest for use in experimental neurophysiological studies. Clinical Relevance: The present results suggest that in humans, epiretinal application of ICG results in prolonged staining of the visual pathway. Therefore, additional studies of long-term toxic effects of ICG on neural cells are warranted before recommending its use in humans as an intraoperative tool for vitreoretinal surgery. [ABSTRACT FROM AUTHOR]

Objective: To examine retinal nerve fiber layer changes with scanning laser polarimetry (SLP) in the eyes of patients with glaucoma and optic disc hemorrhage. Methods: Automated perimetry and SLP were performed in 17 eyes of 17 patients identified prospectively with optic disc hemorrhage. Criteria for visual field progression were based on decreased sensitivity seen at 3 adjacent points on the total deviation plot. Progression on SLP images was defined as a 15% or more decrease in the average thickness of the affected quadrant (superior or inferior), a 25% or more reduction in the affected quadrant ratio, an increase in the nerve fiber analyzer number of 10 or more (GDx Nerve Fiber Analyzer; Laser Diagnostic Technologies), or any change on Serial Analysis of the SLP images. Main Outcome Measures: Visual field progression and SLP image progression. Results: The mean follow-up was 31 months (minimum, 12 months). Of the 17 eyes, 10 (59%) had visual field progression. No significant change was seen on SLP images for either the total group or the group with visual field progression. Five eyes (29%) showed progression on SLP images, 3 of which also showed visual field progression. Ten eyes showed progression on SLP images that was not confirmed on subsequent imaging. Conclusions: In eyes with visual field progression after optic disc hemorrhage, a significant change in the SLP image was not seen. Fluctuation of SLP results in patients with glaucoma necessitates confirmation of progression seen on SLP images. [ABSTRACT FROM AUTHOR]

Objective: To describe the natural history of patients with primary optic nerve sheath meningioma (ONSM) who were cared for without intervention. Methods: A retrospective review of the medical records of 42 patients identified in the database of an academic neuro-ophthalmology unit who had been diagnosed with a unilateral ONSM. Twenty-five had been referred after treatment had been implemented, and 1 was blind at referral. The remaining 16 patients who were followed up with observation only are the focus of this study. Results: The study subjects were followed up for a mean of 6.2 years (range, 2-18 years). The mean follow-up from the time of the first symptom was 10.2 years (range, 3-28 years). No patient died or incurred neurological deficits other than vision loss. At diagnosis, 12 of 16 had a visual acuity of 20/100 or better; 11 had a visual acuity of 20/30 or better. At follow-up, 8 of 16 had a visual acuity of 20/100 or better; 6 had a visual acuity of 20/30 or better. Three patients had slight improvement. Visual fields remained stable in 4 patients and improved in the 3 patients whose visual acuity also improved. Conclusions: Some patients with ONSM have a stable course for many years, and a few may even show slight improvement. The routine application of radiation therapy may unnecessarily expose some patients to complications and should be reserved for those patients whose visual function declines under observation. [ABSTRACT FROM AUTHOR]

Presents several cases related to ophthalmology. Capsular delamination; Optic nerve teratoma; Scleral ulceration after preoperative injection of mitomycin C in the pterygium head.

Background: The observation of a buildup of mitochondria at the level of the lamina cribrosa in the optic nerve head has traditionally been attributed to axoplasmic stasis. However, this region is also the transition zone for myelination, resulting in differing energy requirements. Objective: To investigate the relationship between myelination and mitochondrial activity in optic nerve tissue. Methods: Histological, histochemical, and immunocytochemical techniques were used to demonstrate the distribution of myelin, cytochrome-c oxidase activity, and laminar structure in human optic nerve tissue. A study of rabbit optic nerve and retina and unmyelinated human pituitary stalk was also performed. Cytochrome-c oxidase activity in the human optic nerve tissue was measured using microphotometry. Results: There was a striking inverse relationship between myelination and mitochondrial distribution in all tissue studied. Statistical analysis of microphotometric data showed this distribution to be highly significant. Conclusion: We caution against the previous inference of a process of axoplasmic stasis and suggest that, instead, the distribution of mitochondria reflects the functional requirement of different regions of the ganglion cell axon. Clinical Relevance: Optic neuropathy is associated with several inherited disorders of mitochondria. We suggest that a fine balance exists between energy demand and tissue function in the optic nerve, which may explain why optic nerve pathological features are seen in those with mitochondrial disease. [ABSTRACT FROM AUTHOR]

Objectives: To estimate the measuring depth of the blood flow and to establish the vascular contributions to these measurements with scanning laser Doppler flowmetry (SLDF) of the primate anterior optic nerve. Methods: Optic nerve blood flow in each eye of 8 monkeys was measured using SLDF before and following surgical occlusion of the central retinal artery (n = 4) or posterior ciliary arteries (n = 4). The regional blood flow in both eyes was determined using a nonradioactive microsphere method. Results: The blood flow in the nerve fiber layer (NFL), including the prelaminar region, was measured with microspheres after central retinal artery occlusion; it was significantly reduced (-83%) with no significant change in the combined laminar and retrolaminar regions. The blood flow measured with SLDF had a 51% reduction. After posterior ciliary artery occlusion, the blood flow in the NFL was measured with microspheres and was not significantly affected (+2%); neither was that measured with SLDF (-12%). However, there was a 51% reduction in the laminar and retrolaminar regions when microspheres were used. The mean ± SD tissue thickness of the NFL was 359 ± 16 µm and 353 ± 54 µm in each group. Conclusions: Scanning laser Doppler flowmetry measures blood flow principally in the NFL of the anterior optic nerve, which is primarily supplied by the central retinal artery. Blood flow in the laminar and retrolaminar regions makes a small contribution to the SLDF measurement, with an NFL thickness between 300 and 400 µm. Clinical Relevance: Scanning laser Doppler flowmetry is used for the noninvasive evaluation of ocular microcirculation in diseases such as glaucoma. Because of the dual blood flow supply in the optic nerve and the limited penetration power of the laser, the instrument primarily measures the microcirculation on the surface of the optic nerve, which is largely supplied by the central retinal artery rather than the ciliary arteries. [ABSTRACT FROM AUTHOR]

Objective: To determine whether astrocytes of the human optic nerve head can induce nitric oxide synthase-2 (NOS-2) in response to elevated hydrostatic pressure as a mechanism for directly damaging the axons of the retinal ganglion cells in glaucoma. Methods: Primary cultures of astrocytes from human optic nerve heads were placed in chambers, either pressurized at elevated hydrostatic pressure (60 mm Hg) or maintained at ambient pressure. The induction of NOS-2 was studied by immunocytochemistry, immunoblot, and semiquantitative reverse transcription polymerase chain reaction. Results: In astrocyte cultures under ambient pressure, NOS-2 was almost undetectable. In astrocyte cultures under elevated hydrostatic pressure for 24, 48, and 72 hours, intensive labeling of NOS-2 in the Golgi body and the cytoplasm was observed by immunocytochemistry and intense bands of NOS-2 were detected by immunoblotting. As detected by semiquantitative reverse transcription polymerase chain reaction, the messenger RNA level of NOS-2 increased significantly in the astrocytes under elevated hydrostatic pressure within 12 hours, peaking earlier than the protein level of NOS-2. Conclusion: Elevated hydrostatic pressure induces the astrocytes of the human optic nerve head to express NOS-2. Clinical Relevance: In glaucoma, the appearance of the neurodestructive NOS-2 in astrocytes of the optic nerve head may be a primary response to elevated intraocular pressure, in vivo, and therefore damaging to the axons of the retinal ganglion cells. [ABSTRACT FROM AUTHOR]

Objective: To determine whether there is a difference in central corneal thickness between African American and Caucasian patients. If present, a difference might alter the measurement of intraocular pressure and potentially the assessment and management of glaucoma in these populations. Methods: Central corneal thickness was measured by means of ultrasound pachymetry in African American (n = 56) and Caucasian (n = 32) patients with suspected or confirmed glaucoma and control populations of African American (n = 26) and Caucasian (n = 51) subjects in whom there was no evidence of elevated intraocular pressure or glaucomatous optic nerve damage. Measurements of central corneal thickness were then compared between different subpopulations by means and population distribution analysis. Results: A statistically significant difference was noted between the mean (±SD) central corneal thickness of all African American (including those with and without glaucoma) (right eye, 531.0 ± 36.3 µm; left eye, 530.0±34.6 µm) and all Caucasian (including those with and without glaucoma) (right eye, 558.0±34.5 µm; left eye, 557.6 ± 34.5 µm) patients. Similar results were found when subpopulations were tested. Distribution analysis of central corneal thickness measurements noted the largest cluster of African American patients around 520 to 540 µm, whereas the largest cluster of Caucasian patients was between 580 and 600 µm. Conclusions: African Americans were found to have thinner central cornea thickness measurements than Caucasians. This finding in African Americans may lead to lower applanation intraocular pressure readings compared with those of Caucasians, potentially resulting in an underestimation of the actual level of intraocular pressure. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: To determine optimal scissor blade design and surgical approach to facilitate obtaining a long optic nerve segment during enucleation procedures. Methods: Two hundred mock enucleations were performed with the use of a human child skull model and a silicone sphere to simulate an eye. Temporal and nasal approaches with scissor blades with noncurved, mildly curved, or strongly curved blades were tested. Results: Longer optic nerve segments were obtained with mildly curved scissor blades from both temporal and nasal surgical approaches. Strongly curved scissor blades uniformly produced smaller specimens. Conclusions: Mildly curved scissors should be used for enucleation when a long optic nerve specimen is desired. Strongly curved scissors should be avoided. [ABSTRACT FROM AUTHOR]

Objectives: To determine the morphometric parameters in high-tension glaucoma (HTG) and normaltension glaucoma (NTG) with a confocal scanning laser ophthalmoscope, and to determine the relationship to disc size. Methods: One hundred eighty-six patients with glaucoma were recruited for this study. For each patient, only one eye was randomly chosen. Patients with NTG and HTG were classified using untreated intraocular pressure (IOP) as the variable; the NTG group had tOP less than 22 mm Hg during a diurnal tension curve, while patients with HTG had IOP greater than 21 mm Hg in at least 3 measurements. All the patients were examined with Humphrey perimeter program 30-2 and a Heidelberg Retina Tomograph. Findings were assessed by t test. Patients were then divided by disc area size into 3 subgroups: small discs with an area less than 2 mm², midsized discs with an area of 2 to 3 mm², and large discs with an area greater than 3 mm². Results: One hundred thirty-two HTG eyes and 50 NTG eyes were assessed. Four eyes were excluded because they were classified as having secondary glaucoma. No significant differences were found between HTG and NTG eyes for any Heidelberg Retina Tomograph morphometlic parameters, even when patients were divided into subgroups. Conclusion: No differences were apparent between HTG and NTG in morphometric parameters as measured by scanning laser ophthalmoscopy. [ABSTRACT FROM AUTHOR]

Background: Serum autoantibodies that cross-react with glycosaminoglycans have been proposed to play a significant role in specific tissue injury in patients with systemic autoimmune diseases. Objective: To investigate whether serum immunoreactivity to glycosaminoglycans is present in patients with glaucoma who have aberrant serum autoantibodies to DNA, RNA, nuclear proteins, or retinal proteins, as proteoglycans and their glycosaminoglycan side chains are important components of the optic nerve head and its vasculature. Methods: We performed Western blotting using patient serum samples and human optic nerve head homogenates that were treated with or without specific glycosaminoglycan degrading enzymes. Monoclonal antibodies that recognize different determinants of glycosaminoglycans were used to identify specific substrate antigenicity. We compared the serum immunoreactivity to glycosaminoglycans in 60 age-matched patients with normal-pressure glaucoma, 36 patients with primary open-angle glaucoma, and 20 control subjects by enzyme-linked immunosorbent assay. In addition, immunohistochemistry was performed to compare the distribution patterns of glycosaminoglycans in the optic nerve head of postmortem eyes of agematched patients with normal-pressure glaucoma, primary open-angle glaucoma, and control subjects. Results: Western blotting demonstrated that serum samples from patients with glaucoma who have circulating autoantibodies can recognize optic nerve head proteoglycans, including chondroitin sulfate and heparan sulfate. The level of serum autoantibodies binding purified chondroitin sulfate and heparan sulfate glycosaminoglycans in an enzyme-linked immunosorbent assay was approximately 100% higher in patients with normal-pressure glaucoma than that in control subjects and approximately 50% higher than that in patients with primary open-angle glaucoma. We also observed increased immunostaining of glycosaminoglycans in the optic nerve head of eyes with... [ABSTRACT FROM AUTHOR]

Objective: To determine the foci and duration of protein expression following virus-mediated gene transfer to the optic nerve. Methods: A cytomegalovirus (CMV) promoter was linked to a lacZ-SV40 polyA reporter gene or a humanized green fluorescent protein (hgfp) reporter gene, then inserted into a bacterial plasmid containing adenoassociated virus (AAV) terminal repeat sequences. The CMV-lacZ or the CMV-hgfp construct were injected into the vitreous cavity of strain-13 guinea pigs. Controls consisted of eyes injected with AAV without the promoter and reporter elements or eyes that received no injections. The eyes and optic nerves were processed for β-galactosidase immunohistochemistry and hgfp fluorescence analyses. Cellular transduction at the messenger RNA (mRNA) level was evaluated by in situ reverse transcription-polymerase chain reaction. Results: Weekly fundus photography, done for 1 month, documented the absence of any ocular abnormality due to the viral injections. No in vivo hgfp fluorescence of the retina was visualized. β-Galactosidase histochemical analysis of eye cups that received the lacZ gene construct showed blue lacZ staining of the optic nerve head at 2 weeks. Light microscopy revealed the blue β-galactosidase reaction product in fibers, glial cells, and blood vessels of the optic nerve head and retrobulbar nerve. Histochemistry showed absence of β-galactosidase in the optic nerve at 3 to 12 months, but immunochemistry showed the persistence of β-galactosidase in fibers, glial cells, and blood vessels as late as 1 year after a single ocular injection. In the retina, histochemical staining showed evidence of lacZ at 3 months, but not later. In situ reverse transcription-polymerase chain reaction revealed brown lacZ mRNA reaction product in ganglion cells of the retina. Control eyes that received AAV without the promoter and reporter elements and the eyes that received no viral injections and were processed for &beta... [ABSTRACT FROM AUTHOR]

Blood flow to the retina and optic nerve remains constant over a range of elevated intraocular pressure or mean arterial pressure, independent of sympathetic activation (pressure autoregulation). In addition, increased metabolic activity in these tissues proportionally increases blood flow (metabolic autoregulation). At constant metabolic rate, altered arterial oxygen content reciprocally alters blood flow, leaving total oxygen delivery constant, while blood flow rises and falls with the arterial carbon dioxide tension. These responses are similar to those of the cerebral circulation. However, while aging, atherosclerosis, arterial hypotension, and individual variation may profoundly alter blood flow regulation and predispose to the development of illness, these factors remain largely unexplored. [ABSTRACT FROM AUTHOR]

Objective: To assess the relationship between in vivo measurements of optic disc topography and histomorphometric measurements of optic nerve fiber number in glaucoma. Methods: Both eyes of 10 monkeys (Macaca fascicularis) with laser-induced glaucoma in the right eye were studied. Optic disc topography was measured in vivo with a confocal scanning laser ophthalmoscope. Histomorphometry was performed on optic nerve cross sections using bright-field microscopy with camera lucida. Nerve fiber density was estimated by unbiased random sampling. Nerve fiber number was estimated for each sector by multiplying nerve fiber density with neuroglial area. Nerve fiber count was compared with each of 13 global optic disc topographic parameters. Results: For neuroretinal measurements in the glaucomatous eyes, rim area, retinal nerve fiber layer (RNFL) cross-sectional area, rim volume, and RNFL thickness correlated significantly with optic nerve fiber number. Differences in nerve fiber count between control and glaucomatous optic nerves showed the strongest correlation with differences in mean height contour; this was followed by RNFL cross-sectional area, RNFL thickness, rim volume, and differences in rim area. For cup measurements in the glaucomatous eyes, cup volume below reference, cup area, mean cup depth, the ratio of cup area to disc area, and cup shape correlated significantly with nerve fiber number. Differences in nerve fiber number between control and glaucomatous optic nerves showed the strongest correlation with differences in cup shape; this was followed by mean cup depth, cup volume below reference, the ratio of cup area to disc area, cup area, and differences in cup volume below surface. No association was found between optic nerve fiber number and optic disc area in glaucomatous eyes. Conclusions: In experimental glaucoma, most optic disc topography measures correlated significantly with optic nerve fiber number. The results of this histomorphometric study... [ABSTRACT FROM AUTHOR]

Reports on the case of a 63-year old woman with ocular hypotony. Complains from a painless blurred vision in the left eye; Development of optic disc edema with gross elevation of the optic nerve head, blurred disc margins and choroidal folds consistent with hypotony; Identification of choriotetinal coloboma in the inferonasal equatorial retina.

This article presents the impact of lowering of intraocular pressure (IOP) on the development of glaucoma. Glaucoma is a serious, irreversible but slowly progressive disease. Because the disease affects the peripheral visual field first, it is usually many years from the onset of disease to functional visual loss until the IOP is higher. Even using standard achromatic automated static perimetry, the physician can detect visual-field defects below the level of the defect from the physiologic blind spot. Given the cost of treating all people with ocular hypertension at moderate to high risk of developing glaucoma, it may still be reasonable to wait until the earliest change in the optic nerve or visual field is detected.

Objectives: To quantify and analyze the differences between the length of the optic nerve as measured by the ophthalmologist in the operating room after enucleation and the length as measured by the pathologist after fixation. Methods: The authors performed a retrospective review of patients who underwent either primary or secondary enucleation for retinoblastoma at the Ophthalmic Oncology Center of the New York-Presbyterian Hospital-Cornell campus between November 1979 and August 2001. Intraoperative notes and pathologic reports were reviewed to determine the length of the resected optic nerve as recorded by both the surgeon and pathologist. Results: Sufficient data for inclusion in the study were available from 100 enucleation specimens belonging to 96 patients. A significant degree of shrinkage of the optic nerve occurred after fixation, with a mean shrinkage of 30.3% from the time of enucleation to the time of measurement by the pathologist. Age at enucleation affected the degree of optic nerve shrinkage; nerves from younger children underwent more shrinkage than nerves from older patients. Sex of the patient and the laterality of disease did not significantly affect optic nerve shrinkage. Conclusions: A significant degree of shrinkage of the optic nerve occurs in retinoblastoma enucleation specimens after fixation prior to pathologic analysis. This finding must be taken into account when comparing different series and making recommendations for chemoprophylaxis based solely on histopathologic examination. [ABSTRACT FROM AUTHOR]

The article discusses a case of bilateral foveal neovascularization in a patient with insulin-dependent Diabetes mellitus and provides related photographs. Foveal neovascularization in diabetic retinopathy is rare. Retinal neovascularization in diabetes typically develops along the major temporal vascular arcades, on the optic nerve, or nasal to the optic nerve. Seven cases of unilateral diabetic foveal neovascularization that appeared to originate from perifoveal capillaries have been reported.

Editorial. Comments on the role of genetic testing in glaucoma. Overview of the OcuGene Test; Implications for ophthalmologists; Optic nerve examination.

Reports on the most common manifestation of ocular sarcoidosis which is anterior uveitis. Percentage of patients with sarcoidosis who develop optic nerve involvement; Responsiveness of optic nerve lesions caused by sarcoidosis to steroid therapy with a good visual outcome.