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Biomedical subjects

H A Quigley

Publications and source records attributed to H A Quigley.

At least 37 records · Page 2Linked to original sources
PubMed2000

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.

Acute Disease↗
PubMed2000

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.

Acute Disease↗
PubMed1999

Neuronal death in glaucoma.

Glaucoma is recognized to have its major detrimental effect upon the eye by killing retinal ganglion cells. The process of cell death appears to be initiated at the optic nerve head, though other sites of injury are possible but unsubstantiated. At present the injury at the nerve head seems related to the level of the eye pressure, but its detailed mechanism is as yet unexplained. There is a greater loss of ganglion cells from some areas of the eye, and this feature of glaucoma seems related to the regional structure of the supporting connective tissues of the optic nerve head. Larger retinal ganglion cells have been consistently shown to have somewhat greater susceptibility to injury in glaucoma, though all cells are injured, even early in the process. Ganglion cells die by apoptosis in human and experimental glaucoma, opening several potential areas for future therapies to protect them from dying. Neurotrophin deprivation is one possible cause of cell death and replacement therapy is a potential approach to treatment.

Animals↗
PubMed1999

Neural networks for visual field analysis: how do they compare with other algorithms?

PURPOSE: To compare the performance of a neural network in identifying visual field defects with the performance of other available algorithms. METHODS: A feed-forward neural network with a single hidden layer was trained to recognize visual field defects previously collected in a longitudinal follow-up glaucoma study, and then tested on fields taken from the same study but not used in the training. The receiver operating characteristics of the network then were compared with the previously determined performance of other algorithms on the same data set. RESULTS: At a specificity greater than 90%, the neural network was more sensitive than any of the available algorithms (although only the global indices were available for comparison, as the cluster and cross-meridional algorithms did not achieve such high specificity at their current settings). At a lower specificity (80-85%), the neural network was unable to attain the high sensitivity of the cluster or cross-meridional algorithms; in fact, the cluster algorithm from the Low-Tension Glaucoma study was significantly more sensitive. CONCLUSION: The receiver operating characteristics of a feed-forward neural network designed to detect visual field defects were explored. At a very high specificity (90-95%) a neural network performed better than the global indices. However, at a lower specificity (78%-88%), the neural network performed worse than cluster and cross-meridional algorithms.

Algorithms↗
PubMed1999

Mobility performance in glaucoma.

PURPOSE: To determine whether glaucoma affects mobility performance and whether there is a relationship between mobility performance and stage of disease as estimated from vision-function measures. METHODS: The mobility performance of 47 glaucoma subjects was compared with that of 47 normal-vision subjects who were of similar age. Mobility performance was assessed by the time required to complete an established travel path and the number of mobility incidents. The subjective assessment of falling and fear of falling were also compared. Vision function was assessed by measures of visual acuity, contrast sensitivity, monocular automated threshold perimetry, and suprathreshold; binocular visual fields were assessed with the Esterman test. RESULTS: The glaucoma subjects walked on average 10% more slowly than did the normal-vision subjects. The number of people who experienced bumps, stumbles, or orientation problems was almost twice as high in the glaucoma group than the normal-vision group, but the difference did not reach statistical significance. The difference between groups also was not significant with respect to the number of people who reported falling in the past year (38% for the glaucoma group and 30% for the normal-vision group) or a fear of falling (28% for the glaucoma group and 23% for the normal-vision group). The visual fields assessed with a Humphrey 24-2 test were more highly correlated with walking speed in glaucoma than the visual fields scored by the Esterman scale or than visual acuity or contrast sensitivity. CONCLUSIONS: Glaucoma is associated with a modest decrease in mobility performance. Walking speed decreases with severity of the disease as estimated by threshold perimetry.

Adrenergic beta-Antagonists↗
PubMed1999

The relationship between optic disc area and open-angle glaucoma: the Baltimore Eye Survey.

PURPOSE: To determine if eyes with larger optic disc area are more likely to have open-angle glaucoma or to have glaucoma at lower intraocular pressure (IOP). METHODS: Data were collected from a population-based sample of adults residing in East Baltimore, consisting of demographic information, ocular examinations, automated and static/kinetic visual field tests, IOP as measured by applanation tonometry, and image analysis of the optic disc. Optic disc area was calculated using refractive error to correct magnification. Open-angle glaucoma was defined by visual field and optic disc criteria. One eye from each of 75 patients with glaucoma was compared to those of 3,518 subjects without glaucoma. RESULTS: Although optic disc area was somewhat larger among patients with glaucoma than control subjects, in a regression model adjusting for age, gender, and race, the significance of this difference had a probability of 0.06. Among patients with glaucoma, disc area was not related to IOP level measured at study examination. CONCLUSION: Disc area is a weak risk factor for open-angle glaucoma. Disc area did not differ between patients with glaucoma who had lower IOP and those who had higher IOP among a group with glaucoma that were identified in a population survey.

Adult↗
PubMed1998

Aqueous humor uric acid and ascorbic acid concentrations and outcome of trabeculectomy.

OBJECTIVE: To determine if there is an association between the surgical outcome of trabeculectomy and uric acid and ascorbic acid concentrations in the aqueous humor at the time of the procedure. PATIENTS, MATERIALS, AND METHODS: Aqueous humor samples were collected from the eyes of 169 of 249 adult patients who underwent trabeculectomy alone for any type of glaucoma between April 1989 and July 1995. Postoperatively, all medical records were reviewed and outcomes were classified as successful, unsuccessful, or indeterminate. The ascorbic acid and uric acid concentrations were determined in masked fashion by high-pressure liquid chromatography. Factors associated with surgical outcome were determined. RESULTS: Uric acid concentration was higher in unsuccessful eyes (mean+/-SD, 0.21+/-0.08 mmol/L, n=26) than in successful eyes (0.15+/-0.09 mmol/L, n=91, 95% confidence interval for difference, 0.02-0.10 mmol/L). Ascorbic acid levels were not significantly different in the eyes with unsuccessful (1129.9+/-601.9 micromol/L) and successful (1334.3+/-511.0 micromol/L) surgery (95% confidence interval for difference, -475.2 to 66.4 micromol/L, P=.13) surgery. Other factors associated with failure were previous surgery and surgery performed at the inferior limbus. A multiple polytomous logistic regression analysis was performed, after excluding the small number of operations performed at the inferior limbus. The odds ratio for failure increased by a factor of 1.68 for every 1-mmol/L increase in uric acid (95% confidence interval, 1.16-2.43, P=.006). CONCLUSIONS: Uric acid levels were higher at the time of surgery in eyes that had unsuccessful outcomes than in those with successful outcomes. No significant difference in ascorbic acid levels was detectable. A higher uric acid level in the aqueous humor is a risk factor for trabeculectomy failure and might be tested as a prognostic indicator [corrected].

Aged↗
PubMed1998

Identification of glaucoma-related visual field abnormality with the screening protocol of frequency doubling technology.

PURPOSE: To evaluate the predictive power of frequency doubling technology to distinguish glaucoma suspects from persons with glaucoma visual field loss. METHODS: A consecutive series of 76 subjects referred to a glaucoma service underwent perimetry in one eye with frequency doubling technology in a screening mode and Humphrey 24-2 threshold testing in random order, and had optic disk and clinical nerve fiber layer grading. RESULTS: All subjects performed perimetry with both instruments satisfactorily, with an average test time of 1.8 +/- 0.7 minutes per eye for the frequency doubling technology (instrument time). Of 33 eyes classified as abnormal by glaucoma hemifield test, 91% (30/33) were abnormal on frequency doubling technology (two or more abnormal locations of 17), whereas 94% (31/33) of glaucoma suspects with normal Humphrey fields had normal results with frequency doubling technology. Frequency doubling technology results were highly correlated with Humphrey mean deviation by linear regression (r2 = .74, P = .047) and with corrected pattern standard deviation probability value. A frequency doubling technology error score for each quadrant of the field was highly correlated with the number of severely abnormal points per quadrant in Humphrey threshold tests (r2 = .63, P = .034). There was close agreement between clinical examination of the optic disk and nerve fiber layer and frequency doubling technology results. Three-level quantification of abnormality in frequency doubling technology results did not add to diagnostic accuracy. CONCLUSION: Frequency doubling technology testing shows promise as a screening method in glaucoma.

Aged↗
PubMed1998

Risk factors for noncompliance with glaucoma follow-up visits in a residents' eye clinic.

OBJECTIVE: This study aimed to identify factors associated with compliance with glaucoma follow-up visits. DESIGN: Computer records of a university residents' eye clinic were reviewed to identify a random sample of all persons who had an examination with International Classification of Disease (ICD) 9 coding (ICD9) for glaucoma suspect or glaucoma during a 2-year period (1991-1993) to undergo telephone interview. PARTICIPANTS: Those who were seen at least every 6 months regardless of earlier return instructions were defined as compliant with follow-up (controls, n = 362). Those who had any lapse between visits of longer than 6 months were defined as noncompliant (cases, n = 362). RESULTS: Interviews were completed for 196 cases and 242 controls. Noncompliant persons were significantly more likely to be suspects for glaucoma rather than to have definite glaucoma and to be dissatisfied with waiting time in the clinic (29.1% vs. 17.8%, P < 0.005) and to state that they did not take their glaucoma medications as prescribed (25.4% vs. 13.4%, P < 0.004). They also were less likely to have been prescribed eyedrop medication. A high percentage of both patients and controls knew that glaucoma can lead to blindness (85.2% and 88.4%, respectively). The most common reasons patients gave for not keeping follow-up visits were the perception that their eye problem was "not serious enough," the cost of examinations, and that the doctor did not tell them to come back. CONCLUSION: Compliance with follow-up visits for glaucoma is associated with markers for early disease. Attempts to improve compliance might focus on improved communication of the seriousness of the disease and improvements in clinic waiting time.

Aged↗
PubMed1998

Evaluation of screening schemes for eye disease in a primary care setting.

BACKGROUND AND PURPOSE: Screening in a primary care setting could be an effective method for detection of eye disease. This study was designed to evaluate a questionnaire and a battery of tests for their performance in eye disease screening at a primary care clinic. METHODS: 405 patients aged 40 years or older were interviewed and received a comprehensive eye examination including visual acuity and visual field testing, tonometry, slit-lamp examination, dilated fundus examination and photography. Sensitivity and specificity for the identification of eye disease were calculated for each test and various combinations of tests. RESULTS: A questionnaire-based algorithm for detection of overall eye disease was sufficiently sensitive (90%) but less specific (44%) than an ideal screening test. Distance visual acuity with presenting correction of < or = 20/40 had a sensitivity of 61% and specificity of 72%. A dilated fundus examination had a sensitivity of 79% and specificity of 82%. In screening for glaucoma, tonometry was ineffective (sensitivity = 27% and specificity = 96%), while visual field testing by suprathreshold screening had a sensitivity of 70% and specificity of 67%. Among a variety of combinations, a two-stage strategy with the questionnaire as a first-stage and visual acuity and ophthalmoscopy as second-stage tests provided the best balance of sensitivity (83%) and specificity (76%). CONCLUSION: Among currently available ophthalmic tests, an eye examination including a thorough fundus examination is critical in detection of eye disease. A five-item questionnaire may be useful to identify patients at high risk in primary care practice. More effective tests are needed to improve performance of eye disease screening.

Adult↗
PubMed1998

The efficacy of the dicon screening field to detect eyes with glaucomatous field loss by Humphrey threshold testing.

PURPOSE: The authors compare the results of the Dicon suprathreshold, kinetic fixation perimeter with multiple stimulus presentation to automated threshold perimetry (Humphrey) in the same eye. METHODS: A Dicon screening visual field test and a Humphrey threshold visual field test were performed in 148 eyes of 148 persons with glaucoma or who were suspect for glaucoma. The number and pattern of missed points on the Dicon test were compared with Humphrey global indices in each eye. RESULTS: The median time to complete the 40-point, Dicon suprathreshold test was 2.7 minutes per eye. Regression analyses indicated that Dicon test parameters were modestly correlated with Humphrey corrected pattern standard deviation (CPSD) probability and mean deviation (R2 ranging from 0.21 to 0.46, p = 0.000). With glaucoma defined as a Humphrey Glaucoma Hemifield Test (GHT) result of outside normal limits, the best mix of sensitivity and specificity of Dicon results occurred at 2 or more missed points, with sensitivity of 64% and specificity of 83%. The specificity was maximum (90%) with a Dicon criterion of 3 or more adjacent missed points, but sensitivity at this level was 55%. With glaucoma defined by CPSD probability value less than 1%, sensitivity and specificity for two adjacent missed Dicon points were 69% and 87%, respectively. CONCLUSION: Dicon suprathreshold testing is a practical means to differentiate between some persons with glaucomatous damage and glaucoma suspects.

Adult↗
PubMed1997

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.

Aged↗
PubMed1997

Effect of cataract extraction on the results of automated perimetry in glaucoma.

OBJECTIVE: To investigate the effect of cataract extraction on the results of automated perimetry in persons with glaucomatous visual field loss. SUBJECTS: Subjects from a retrospective study of visual field progression who underwent cataract extraction during follow-up were identified. Subjects came from the glaucoma service of a hospital-based tertiary referral center. METHODS: Subjects had at least 7 Humphrey 24-2 or 30-2 visual fields over 5 years or more, with an abnormal glaucoma hemifield test result on the first 2 examinations. Visual field data were transferred to a microcomputer and comparison of the visual fields immediately before and after cataract extraction was performed. RESULTS: Sixty-five eyes of 50 subjects (mean age, 71.8 years) were included in the analysis. A mean improvement in mean deviation (MD) of 1.68 dB (P<.001), and a mean worsening in corrected pattern SD (CPSD) of 0.54 dB (P=.09) was observed. The mean unweighted change in threshold in the 52 points of program 24-2 was 1.58 dB, corresponding to a 43.9% increase in sensitivity. A significant correlation between improvement in visual acuity and improvement in MD was also found. A mean increase in CPSD of 1.61 dB (P=.005) occurred in subjects with dense scotomas (minimum threshold value < or = 5 dB) and preoperative CPSD of 8 dB or less. CONCLUSIONS: In persons with glaucomatous visual field defects, cataract extraction produces only a modest improvement in MD. After cataract surgery, the CPSD index worsened in many subjects with dense scotomas. This suggests that the development of cataract can mask progressive glaucomatous visual field loss in such persons.

Aged↗