Comparison of end-tidal carbon monoxide measurements with direct antiglobulin tests in the management of neonatal hyperbilirubinemia.

OBJECTIVE: Determine whether management of neonatal hyperbilirubinemia differs if one used end-tidal carbon monoxide (CO) corrected for ambient CO (ETCOc) measurements instead of direct antiglobulin test (DAT) results to assess the severity of hemolysis. STUDY DESIGN: Retrospective chart review of infants with total bilirubin and ETCOc levels measured from July 2016 to August 2018. The reported treatment is the hypothetical management infants might have received had there been strict adherence to American Academy of Pediatrics guidelines, rather than the actual management they received. RESULT: Only 27.2% of 191 DAT(+) infants were hemolyzing based on ETCOc, while 29.1% of DAT (-) infants were hemolyzing based on ETCOc. Management of 18 (9.4%) infants differed depending if ETCOc or DAT were used to determine hemolysis. Eight fewer infants would have received phototherapy if ETCOc was used. CONCLUSIONS: ETCOc is a more accurate determinant of hemolysis in the newborn, and its use can lead to less phototherapy.

Alterations in the expression of interleukin-2R subunits by activated T cells from elderly humans are uncoupled from aberrancies in G1/S progression.

Activated T cells from elderly humans are known to often display a decline in interleukin-2 (IL-2) production. However, the possible effects of aging on the expression of IL-2 receptor (IL-2R) subunits by human T cells are more controversial and less well characterized. In the present investigation, the surface expression of IL-2Ralpha, IL-2Rbeta, and IL-2Rgamma subunits on resting and activated T cells from 15 sets of elderly and young humans was evaluated. The results showed no significant differences in the average expression of IL-2Ralpha, IL2Rbeta, and IL-2Rgamma on resting T cells from elderly and young subjects, with values of 10% or less. Similarly, no significant differences were found in the mean levels of IL-2Ralpha, IL-2Rbeta, and IL-2Rgamma on T cells from elderly and young subjects stimulated with anti-Ig cross-linked anti-CD3 (monoclonal antibody [mAb] OKT3), phorbol myristate acetate (PMA), anti-CD3 and PMA, or 1% phytohemagglutinin (PHA) plus PMA. Analyses of the expression of IL-2R on activated T cells from elderly people revealed a marked heterogeneity in IL2R levels irrespective of the stimuli. Other experiments showed that the age-related alterations in surface expression of IL-2Ralpha were not correlated to changes in the release of soluble IL-2Ralpha. Age-related changes in IL-2R expression on activated T cells from individual donors were not coupled to the ability of the T cells to undergo G(1)/S progression. Collectively, these observations suggest that activated T cells from elderly people exhibit substantial heterogeneity in the expression of IL-2R subunits and that alterations in IL-2R expression may be distinct from intrinsic defects in G(1)/S progression and proliferative responses.

Optic nerve transection in monkeys may result in secondary degeneration of retinal ganglion cells.

PURPOSE: Interest in neuroprotection for optic neuropathies is, in part, based on the assumption that retinal ganglion cells (RGCs) die, not only as a result of direct (primary) injury, but also indirectly as a result of negative effects from neighboring dying RGCs (secondary degeneration). This experiment was designed to test whether secondary RGC degeneration occurs after orbital optic nerve injury in monkeys. METHODS: The superior one third of the orbital optic nerve on one side was transected in eight cynomolgus monkeys (Macaca fascicularis). Twelve weeks after the partial transection, the number of RGC bodies in the superior and inferior halves of the retina of the experimental and control eyes and the number and diameter of axons in the optic nerve were compared by detailed histomorphometry. Vitreous was obtained for amino acid analysis. A sham operation was performed in three additional monkeys. RESULTS: Transection caused loss of 55% +/- 13% of RGC bodies in the superior retina of experimental compared with fellow control eyes (mean +/- SD, t-test, P < 0.00,001, n = 7). Inferior RGCs, not directly injured by transection, decreased by 22% +/- 10% (P = 0.002). The loss of superior optic nerve axons was 83% +/- 12% (mean +/- SD, t-test, P = 0.0008, n = 5) whereas, the inferior loss was 34% +/- 20% (P = 0.02, n = 5). Intravitreal levels of glutamate and other amino acids in eyes with transected nerves were not different from levels in control eyes 12 weeks after injury. Fundus examination, fluorescein angiography, and histologic evaluation confirmed that there was no vascular compromise to retinal tissues by the transection procedure. CONCLUSIONS: This experiment suggests that primary RGC death due to optic nerve injury is associated with secondary death of surrounding RGCs that are not directly injured.

Retrograde axonal transport of BDNF in retinal ganglion cells is blocked by acute IOP elevation in rats.

PURPOSE: To determine whether acute experimental glaucoma in rats obstructs retrograde transport of brain-derived neurotrophic factor (BDNF) to retinal ganglion cells (RGCs). METHODS: Forty rats had unilateral injection of either (125)I-BDNF (20 animals) or a mixture of (125)I-BDNF and 100-fold excess nonradiolabeled BDNF (20 animals). In each group of 20 animals, eyes contralateral to injection had either normal intraocular pressure (IOP; 10 animals) or IOP elevated to 25 mm Hg below the systolic blood pressure of the eye (10 animals). In each group of 20 rats, ipsilateral eyes had IOP set at systolic blood pressure (4 eyes), had optic nerve transection (10 eyes), or had normal IOP (6 eyes). Six hours after injection, animals were killed and tissues were fixed, embedded, and sectioned for autoradiography. Grain counts were performed over retina and optic nerve using automated image analysis. RESULTS: IOP elevation to 25 mm Hg below systolic blood pressure (perfusion pressure [PP] 25) decreased median retinal nerve fiber layer (NFL) grains by 38% compared with controls (P: < 0.001). Competition by cold BDNF reduced NFL grains by 28% (P: = 0.013). Considering only the radioactivity representing specific retrograde transport of BDNF, IOP elevation to PP25 reduced transport by 74%, whereas elevation to PP0 (equaling systolic blood pressure) reduced specific transport by 83%. CONCLUSIONS: BDNF is transported retrogradely from the superior colliculus in adult rats, and this transport is substantially inhibited by acute IOP elevation. Deprivation of BDNF among RGCs may contribute to neuron loss in glaucoma.

Number of ganglion cells in glaucoma eyes compared with threshold visual field tests in the same persons.

PURPOSE: To compare the number of retinal ganglion cells (RGCs) topographically mapped with specific visual field threshold test data in the same eyes among glaucoma patients. METHODS: Seventeen eyes of 13 persons with well-documented glaucoma histories and Humphrey threshold visual field tests (San Leandro, CA) were obtained from eye banks. RGC number was estimated by histologic counts of retinal sections and by counts of remaining axons in the optic nerves. The locations of the retinal samples corresponded to specific test points in the visual field. The data for glaucoma patients were compared with 17 eyes of 17 persons who were group matched for age, had no ocular history, and had normal eyes by histologic examination. RESULTS: The mean RGC loss for the entire retina averaged 10.2%, indicating that many eyes had early glaucoma damage. RGC body loss averaged 35.7% in eyes with corrected pattern SD probability less than 0.5%. When upper to lower retina RGC counts were compared with their corresponding visual field data within each eye, a 5-dB loss in sensitivity was associated with 25% RGC loss. For individual points that were abnormal at a probability less than 0.5%, the mean RGC loss was 29%. In control eyes, the loss of RGCs with age was estimated as 7205 cells per year in persons between 55 and 95 years of age. In optic nerves from glaucoma subjects, smaller axons were significantly more likely to be present than larger axons (R2 = 0.78, P<0.001). CONCLUSIONS: At least 25% to 35% RGC loss is associated with statistical abnormalities in automated visual field testing. In addition, these data corroborate previous findings that RGCs with larger diameter axons preferentially die in glaucoma.

Obstructed axonal transport of BDNF and its receptor TrkB in experimental glaucoma.

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.

Multiple endocrine neoplasia type 2A: a 25-year review.

BACKGROUND/PURPOSE: Before 1970, treatment decisions for the thyroid lesions in patients with multiple endocrine neoplasia (MEN) were based on physical findings. For the next 20 years, biological markers assumed a preeminent role, and at present, DNA testing is being used to define the need for therapeutic intervention. This report presents a 25-year review of 22 children with MEN-2A, with a mean follow-up of 12.5 years. METHODS: All 22 children underwent a total thyroidectomy, and four (18%) were rendered permanently hypoparathyroid. Since 1976, however, only one patient (6.7%) has lost parathyroid function. Despite the fact that biological screening studies routinely were performed once a year in the majority of our patients and surgery was recommended for any elevation in the serum calcitonin (CT) levels, medullary carcinoma of the thyroid (MTC) developed in 17 children (77%) and only five had C cell hyperplasia (CCH). Thirteen of the 17 had macroscopic tumor described by the pathologist, evidence of recurrent disease (MTC-REC) has developed in four children (24%). RESULTS: There was considerable overlap in both the basal and stimulated CT levels among the five children with CCH, the 13 with localized MTC (MTC-NED), and the four who later had recurrent MTC. The basal calcitonin levels were between 25 and 110 (mean, 58) in the CCH patients, 30 to 1,130 (mean, 184) in the MTC-NED group, and 108 to 201 (mean, 140) in those with recurrent MTC. The corresponding stimulated calcitonin levels were 45 to 417 (mean, 179) in CCH, 111 to 9,510 (mean, 1,407) in MTC-NED, and 449 to 5,093 (mean, 3,383) in MTC-REC. CONCLUSIONS: (1) Basal and pentagastrin-stimulated CT levels did not reliably discriminate between CCH and MTC and should not be used to define the timing of thyroid surgery in children with MEN-2A. (2) Surgical therapy should be undertaken early in childhood on the basis of molecular genetic testing. (3) Postoperative complications are infrequent in the modern era.

Redox signals and NF-kappaB activation in T cells.

Accumulating data from a number of laboratories have recently indicated that the response of transcription factor NF-kappaB to alterations in the redox homeostasis of cells may play an important role in modulating immune function. The activation of NF-kappaB has been recognized to regulate a number of genes necessary for normal T cell responses including IL-2, IL-6, IL-8, and several T cell surface receptors. Diminished NF-kappaB activity has been shown to occur in T cells with aging, suggesting that impaired activation of NF-kappaB might occur during cellular senescence. In addition, aberrancies in NF-kappaB activity have been implicated in the immunopathogenesis of diseases involving immune or inflammatory processes such as atherosclerosis and HIV-1 infection. The role of H2O2 and other reactive oxygen species (ROS) as an integratory secondary messenger for divergent T cell signals has been complicated by the fact that various T cell lines and peripheral blood T cells differ markedly in the levels of NF-kappaB activation induced by oxidant stress. Additionally, proposed pathways of NF-kappaB activation have been based on indirect evidence provided by experiments which used antioxidants to inhibit active NF-kappaB formation. Further, complete activation of T cells requires at least two signals, one that stimulates an increase in intracellular calcium and one that stimulates enzymatic processes including kinases. Similarly, substantial evidence indicates that full activation of NF-kappaB requires dual signals. The ability of H2O2 or other ROS to induce T cell signals and functional responses by these two mechanisms is reviewed and the specific response of NF-kappaB to redox changes in T cells is examined. Data are also presented to suggest that the redox regulation in NF-kappaB activation may be relevant to immune-related diseases and to aging.

TUNEL-positive ganglion cells in human primary open-angle glaucoma.

OBJECTIVE: To determine whether retinal ganglion cell death in primary open-angle glaucoma occurs by apoptosis. METHODS: Eighteen eyes of 17 subjects with documented primary open-angle glaucoma were compared with 21 control eyes that were group matched for age, race, and sex. Staging of glaucoma severity was performed by histologic optic nerve evaluation. Fixed, paraffin-embedded retinal sections were assayed by the TUNEL (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate (UTP)-biotin nick end-labeling) method to detect the internucleosomal DNA fragmentation that is characteristic of apoptosis. RESULTS: A positive TUNEL reaction was observed among ganglion layer cells in 10 of 18 cases with glaucoma, compared with 1 of 11 control cases without confounding systemic disease (5 control eyes were excluded owing to artifactual staining and 4 eyes had confounding systemic disease). Sections containing more than 250,000 cells in the ganglion cell layer were examined in cases and controls. The frequency of TUNEL-positive cells in the ganglion cell layer in cases with glaucoma was 1.76 per 10,000, or 15.2 times greater than the control frequency from individuals without confounding disease (P < .001; 95% CI, 2.46-623). Eyes without glaucoma from subjects with diabetes and amyotrophic lateral sclerosis showed more positive cells than other controls. CONCLUSION: Apoptosis seems to be a mechanism of cell death in human eyes with primary open-angle glaucoma.

Prognostic classification for esophageal atresia and tracheoesophageal fistula: Waterston versus Montreal.

Since 1962, the Waterston classification has been used to stratify neonates who have esophageal atresia (EA) and/or tracheoesophageal fistula (TEF) into prognostic categories based on birth weight, the presence of pneumonia, and the identification of other congenital anomalies. In response to advances in neonatal care, the surgeons from the Montreal Children's Hospital proposed a new categorization system in 1993 in an attempt to define the current risk factors for patients who have EA/TEF. In the Montreal experience only two characteristics independently affected survival: preoperative ventilator dependence and associated major anomalies. The goal of this study was to determine which system had the greatest validity for the evaluation of prognosis in our patients with EA/TEF. The charts of 94 patients who had EA/TEF treated between 1972 and 1991 were reviewed. Patients were classified using both the Waterston and Montreal systems. Groups were compared with Fisher's Exact test using a 95% confidence level for statistical significance. Eleven infants were ventilator dependent preoperatively; 62 children had major associated anomalies, 8 of which were considered life threatening. Sixteen children died within 4 years, eight during their initial hospital stay. Five of the eight early postoperative deaths occurred in the highest-risk patients (Waterston C or Montreal II). Analysis was performed for multiple risk factors and mortality. As in the Montreal study, the presence of life-threatening and major congenital anomalies represented significant risk factors for death. Pulmonary disease as delineated by ventilator dependence appeared to be more accurate than pneumonia. This study confirms the accuracy of the Montreal classification in defining prognosis for EA/TEF. The Montreal system more accurately identifies children at highest risk than the Waterston classification.

Pulmonary function is compromised in children with mediastinal lymphoma.

PURPOSE: Lymphomas account for nearly 20% of the malignancies in childhood and the majority of patients with Hodgkin's Disease (HD) and non-Hodgkin's lymphoma (NHL) have radiological evidence of mediastinal involvement at presentation. Children with mediastinal tumors are at risk for the development of lethal airway obstruction during general anesthesia. This study quantitates the degree of the airway obstruction and the functional significance of tracheal compression in a cohort of 51 children with HD and NHL. RESULTS: Thirty patients with HD (mean age, 14.6 years) and 21 with NHL (mean age, 9.2 years) were included in this study. Twenty-five children (49%) had respiratory symptoms at the time of presentation. Respiratory complaints were much more common in children with NHL (76%) when compared with those with HD (30%). Pulmonary function was also significantly worse in the NHL patients who had a mean upright forced vital capacity (FVC) of 66 +/- 21%. The comparable value for the children with HD was 85 +/- 15% (P = .031). Patients with respiratory symptoms at presentation had both obstructive and restrictive deficits of pulmonary function. Their mean upright forced expiratory volume in 1 second (FEV1) was 69 +/- 22% and the FVC was 69 +/- 18%. Children with large mediastinal masses also had significantly decreased pulmonary function compared with those with small tumors. The upright FEV1 for these two groups was 72 +/- 18% versus 98 +/- 15% (P = .016). Their FVC values were 68 +/- 20% and 91 +/- 17%, respectively (P = .049). Mean tracheal compression was measured at 44% in the children with large tumors versus 27% for those with small lesions (P = .048). CONCLUSION: Children with mediastinal lymphomas have both obstructive and restrictive deficits on pulmonary function testing. Pulmonary function is significantly decreased in patients with NHL, children who present with respiratory symptoms, and those with very large mediastinal masses (mediastinal mass ratio > 45%). The extent of tracheal compression correlates with the size of the mediastinal mass.

Quantitative studies of elastin in the optic nerve heads of persons with primary open-angle glaucoma.

PURPOSE: To compare quantitative and qualitative differences in elastin content in the optic nerve heads of glaucomatous and control human eyes. METHODS: Transmission electron microscopy and quantitative histomorphometry on ten control and ten glaucomatous eyes. RESULTS: Elastin fiber complexes in the control lamina cribrosa were smaller and more numerous than in the insertion zone of the sclera immediately surrounding the lamina. Although the density of elastin fibers in the normal lamina was twice that of the insertion zone (P = 0.004), the percent area of the connective tissue matrix occupied by elastin was the same for both zones (P > 0.4). There was no difference between control and glaucomatous eyes in the quantified parameters of elastin content or in the ultrastructure of elastin between control and glaucomatous eyes. CONCLUSIONS: The authors demonstrated for the first time that elastin in the normal lamina consists of fibers of smaller diameter than in the adjacent sclera, although the total amount of elastin is similar in both locations. This may provide maximum viscoelasticity within the limited connective tissue beam area of the lamina. Despite using a large number of specimens, the authors again found no differences between normal and glaucomatous eyes in the number or ultrastructural appearance of elastin fibers.

Optimal NF kappa B mediated transcriptional responses in Jurkat T cells exposed to oxidative stress are dependent on intracellular glutathione and costimulatory signals.

Many early response genes induced by the exposure of mammalian cells to environmental stress contain DNA sequences which bind nuclear factor (NF) kappa B. However, the effects of oxidative stress on NF kappa B activity in T cells are contradictory with evidence supporting both stimulation and suppression. The present investigation examined the effects of low levels of oxidative stress in the form of H2O2 on NF kappa B transactivation in Jurkat T cells and the regulation of NF kappa B activity by cellular glutathione (GSH) levels and costimulatory signals. Transient transfection analyses demonstrated 2-3 fold increases in transcription of an NF kappa B dependent chloramphenicol acetyl transferase (CAT) reporter after the exposure of Jurkat cells to 100-500 microM H2O2. By comparison, dual stimulation of Jurkat cells with phytohemagglutinin (PHA) plus phorbol (PMA) induced 9-10 fold increases in NF kappa B CAT activity. Although no marked changes in GSH levels were detected in cells treated with H2O2 or PHA/PMA, the depletion of GSH in cells pretreated with DL-buthionine-[S,R]-sulfoximine (BSO) substantially inhibited NF kappa B transactivation by H2O2. In addition, H2O2 was less effective than PHA/PMA in inducing NF kappa B1 (p50)/RelA (p65) complexes. However, signals induced by oxidative conditions effectively cooperated with stimulatory signals provided by PMA but not with T cell receptor/CD3 stimulation to induce significant increases in NF kappa B CAT responses. These results suggest that a functional GSH system is required for NF kappa B activation in T cells exposed to oxidative reagents and provide evidence that oxidative stress triggers signaling events capable of participating with distinct coregulatory signals to activate NF kappa B transcriptional responses.

Change in the optic disc and nerve fiber layer estimated with the glaucoma-scope in monkey eyes.

PURPOSE: The purpose of this research was to measure quantitatively changes in the position of the optic disc and nerve fiber layer during acute and chronic experimental conditions simulating glaucoma in monkey eyes. METHODS: The positions of the surface of the optic disc and peripapillary nerve fiber layer were imaged in cynomolgus monkey eyes with the Glaucoma-Scope. Acute intraocular pressure changes was produced by anterior chamber cannulation. Chronic change was induced by trabecular laser scarring leading to chronic experimental glaucoma and by orbital transection of the optic nerve. RESULTS: Mean backward movements of the disc surface of 50-60 microns were detected when intraocular pressure was elevated to 45 mm Hg for 45 min. The disc position reverted in viscoelastic fashion toward its original location on normalization of pressure. Loss of nerve fibers induced by elevated intraocular pressure was more closely related to change in the mean position of the disc (MPD) than to change in cup/disc ratio. Chronic glaucoma led to much deeper excavation of the disc than experimental optic atrophy, but peripapillary atrophy was similar in the two conditions with the index, nerve fiber layer area, whose values correlate well with the number of nerve fibers in an eye that is estimated histologically (r2 = 0.75, p = 0.003, n = 9). CONCLUSION: The optic disc behaves in visco-elastic manner with change in intraocular pressure Composite data indices that represent the mean surface topography of the disc and peripapillary region can be used to estimate the degree of glaucoma damage.

Pediatric cervical-spine immobilization: achieving neutral position?

This study was designed to evaluate prospectively the ability of current spine-immobilization devices to achieve radiographic-neutral positioning of the cervical spine in pediatric trauma patients. All trauma patients who required spinal immobilization and a lateral cervical spine radiograph were included in the study. A lateral cervical spine radiograph was obtained while the child was immobilized. The Cobb angle (C2-C6) was measured using a handheld goniometer. The method of immobilization, age at injury, and Cobb angle were compared. One hundred and eighteen patients with an average age of 7.9 years were enrolled. The majority were males (71%). The most frequent mechanisms of injury included motor vehicle accidents (35%) and falls (32%). The average Glascow Coma Scale score was 14. Although 31% of the children complained of neck pain, 92% were without neurologic deficits. The Cobb angles ranged from 27 degree kyphosis to 27 degree lordosis, and only 12 of the patients presented in a neutral position (0 degrees). Greater than 5 degrees of kyphosis or lordosis was observed in 60% of the children. Thirty-seven percent of the patients had 10 degrees or greater angulation. The most frequent methods of immobilization included a collar, backboard, and towels (40%), and a collar, backboard, and blocks (20%), but these techniques provided < 5 degrees kyphosis or lordosis in only 45% and 26% of the children respectively. No single method or combination of methods of immobilization consistently placed the children in the neutral position.(ABSTRACT TRUNCATED AT 250 WORDS)

Retinal ganglion cell death in experimental glaucoma and after axotomy occurs by apoptosis.

PURPOSE: To investigate whether retinal ganglion cell death in experimental glaucoma and after axotomy occurs by apoptosis. METHODS: Chronic elevated eye pressure was produced in 20 monkey eyes, and the optic nerve was transected unilaterally in the orbit of 10 monkeys and 14 rabbits. Sixteen monkey and 14 rabbit eyes were studied as normal controls. Analytic methods included light and electron microscopy, histochemistry for DNA fragmentation (TUNEL method), and DNA electrophoresis in agarose gels. RESULTS: Dying ganglion cells in the experimental retinas exhibited morphologic features of apoptosis, including chromatin condensation and formation of apoptotic bodies. Cells with a positive reaction for DNA fragmentation were observed in eyes subjected to axotomy and experimental glaucoma but were only rarely encountered in control eyes. No evidence of internucleosomal fragmentation was detected electrophoretically, possibly because of the small proportion of cells that were dying at any given time. CONCLUSION: Some retinal ganglion cells injured by glaucoma and by axotomy die by apoptosis.

Primary open-angle glaucoma is not associated with photoreceptor loss.

PURPOSE: To determine if photoreceptors die in primary open-angle glaucoma. METHODS: Retinas were examined in a masked fashion from nine standard locations of 14 eyes with documented open-angle glaucoma and from nine age-matched control eyes. The number and density of photoreceptors, as well as the area and height of the outer nuclear layer, were calculated with an automated image analysis system. The number of photoreceptors per 0.1 mm of retina was determined. RESULTS: No significant difference was seen between control and glaucomatous eyes in comparisons of photoreceptor density, outer nuclear layer height, or photoreceptors per 0.1 mm of retinal length in nine retinal zones. There was no detectable association between photoreceptor number and severity of glaucoma (defined as mild, moderate, or severe), visual field, and optic nerve fiber loss. In eyes in which damage predominated in the upper or lower visual field, no corresponding difference in photoreceptor number in upper compared to lower retinal zones was observed. CONCLUSION: Photoreceptors are not lost in substantial numbers in primary open-angle glaucoma.

A clinical study of peripapillary crescents of the optic disc in chronic experimental glaucoma in monkey eyes.

OBJECTIVE: We produced chronic experimental glaucoma in 41 monkey eyes and assessed the long-term effects of elevated intraocular pressure on the presence of, and changes in, peripapillary crescents. METHODS: Three readers independently plotted peripapillary crescent size and location using stereo fundus photographs before and after chronic elevation of intraocular pressure in 41 monkey eyes. RESULTS: Crescents were found in a majority of normal eyes. After chronically elevated intraocular pressure, new peripapillary crescents developed in only two eyes. Using planimetric analysis, crescent size was enlarged in five (22%) of the 23 eyes with preexisting crescents. Preexisting crescents became more apparent without change in size in a majority of eyes (reader A, 15 [68%] of 22 eyes; reader B, 17 [74%] of 23 eyes; and reader C, 13 [68%] of 19 eyes). CONCLUSIONS: We conclude that peripapillary crescents are often present in normal monkey eyes but that they do not often undergo dramatic changes in size with chronic intraocular pressure elevation. The presence of a crescent was not significantly associated with the development of optic disc cup enlargement in the experimental monkey eye.

Change in the appearance of elastin in the lamina cribrosa of glaucomatous optic nerve heads.

Elastin fibers in the lamina cribrosa of glaucoma eyes have a curled appearance when the tissue is fixed at atmospheric pressure. To evaluate the effect of preparation conditions on elastin appearance, we set the eye pressure at one of four levels during tissue fixation in 18 glaucoma and 16 normal eyes. Glaucomatous damage was associated with an abnormal appearance of elastin at each pressure level. The majority of glaucoma eyes (11/18) had curled elastin profiles. In glaucoma eyes with definite nerve damage, elastin was graded moderately or severely abnormal in 47% (7/15), while in normal controls the rate of similar curling was 6% (1/16). The severity of abnormal elastin appearance was lower in glaucoma eyes that were fixed and frozen at higher intraocular pressures, but the difference was not statistically significant.

Global and regional detection of induced optic disc change by digitized image analysis.

OBJECTIVE: To evaluate two new strategies for the detection of optic disc change within individual eyes by digitized image analysis. METHODS: Eleven normal optic discs of 11 monkeys were imaged with a digital imaging system (Topcon Imagenet, Topcon Instrument Corporation of America, Paramus, NJ) at two intraocular pressures (10 and 45 mm Hg). To detect global change in the disc, we compared conventional optic disc parameters with a new optic disc parameter: mean position of the disc. To detect regional change, the 95% confidence interval for change was calculated for each data point and mapped for each disc. RESULTS: Posterior deformation of the disc surface was detected in seven of 11 eyes using conventional parameters and in 10 of 11 eyes using mean position of the disc. Regions of posterior deformation were detected by 95% confidence interval for change mapping in all 11 discs as localized areas of confluent, posteriorly displaced points. CONCLUSIONS: Mean position of the disc outperformed conventional measurements in the detection of global optic disc change. Ninety-five percent confidence interval for change mapping may allow individual data point-based focal and regional analysis of the disc.