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Biomedical subjects

H A Quigley

Publications and source records attributed to H A Quigley.

At least 19 recordsLinked to original sources

Changes in optic disk characteristics and number of nerve fibers in experimental glaucoma.

We compared the change in cup/disk ratio and neuroretinal rim area-to-disk area to estimated change in the number of optic nerve fibers in 12 cynomolgus monkeys with unilateral experimental glaucoma. Changes in the cup/disk ratios and neuroretinal rim area-to-disk area were estimated from stereoscopic optic disk photographs that were obtained before and after the development of increased intraocular pressure. Change in the number of optic nerve fibers in the glaucomatous nerves was estimated by comparing them to their fellow normal nerves. A significant linear correlation was present between change in the cup/disk ratios and neuroretinal rim area-to-disk area, and estimated change in the number of optic nerve fibers (r > or = .85; P < .0002). In optic disks with initial cup/disk ratios of 0.2 to 0.3 and neuroretinal rim area-to-disk area of 0.9, an increase in the cup/disk ratio of 0.1 and a decrease of 0.1 in the neuroretinal rim area-to-disk area is associated with a 10% and 9% loss of optic nerve fibers, respectively.

Animals

A whole-field scotopic retinal sensitivity test for the detection of early glaucoma damage.

We designed and evaluated a new test for the detection of early glaucoma damage in 133 persons who were classified as normal, suspected of having glaucoma, or having glaucoma. The test stimulates the entire visual field with a flashing white light under dark-adapted conditions. It can be performed easily by a high proportion of subjects and is as reproducible as present psychophysical tests. Glaucomatous eyes were discriminated from normal with a diagnostic power of 0.91 as judged by receiver operating characteristic analysis, and specificity and sensitivity were 91% and 86%, respectively. Glaucoma suspects with an abnormal response to the whole-field scotopic test were more likely to have other signs indicating early optic nerve injury, including a greater proportion of borderline field defects, nerve fiber layer defects, or glaucomatous fellow eyes. Assessment of whole-field scotopic sensitivity may be useful in glaucoma screening.

Adult

An evaluation of optic disc and nerve fiber layer examinations in monitoring progression of early glaucoma damage.

From annual examinations of 813 ocular hypertensive eyes, the authors compared optic disc and nerve fiber layer photographs in 2 age-matched subgroups: 37 eyes that converted to abnormal visual field tests at the end of a 5-year period and 37 control eyes that retained normal field tests. Disc change was detected in only 7 of 37 (19%) converters to field loss and in 1 of 37 (3%) controls. Progressive nerve fiber layer atrophy was observed in 18 of 37 (49%) converters and in 3 of 37 (8%) controls. Serial nerve fiber layer examination was more sensitive than color disc evaluation in the detection of progressive glaucoma damage at this early stage of glaucoma. The evaluation of cup-to-disc ratio or of the nerve fiber layer appearance in the initial photograph taken 5 years before field loss were equally predictive of future field damage. The position of nerve fiber layer defects was highly correlated with the location of subsequent visual field loss.

Aged

Effect of topical mitomycin C on glaucoma filtration surgery in monkeys.

In this study, an experimental model of glaucoma filtration surgery was used to evaluate the clinical and histologic effects of a single intraoperative topical application of mitomycin C. Argon laser treatment to the trabecular meshwork produced sustained elevation of intraocular pressure in monkeys. Eight eyes of four animals were randomly assigned to receive topical mitomycin C or balanced salt solution at the time of full-thickness sclerostomy. Surgical success was substantially increased in four of five eyes that received mitomycin C when compared with three eyes that received topical balanced salt solution. Mitomycin C was also effective in prolonging surgical success in two eyes that had previously undergone surgery and failed. No significant ocular toxicity was observed in eyes treated with mitomycin C. Histologic examination of mitomycin C-treated eyes showed patent sclerostomies and hypocellular, well-formed bleb cavities. A single intraoperative application of mitomycin C has a marked effect on postoperative wound healing after filtration surgery in monkeys.

Administration, Topical

A comparison of the OKP visual field screening test with the Humphrey field analyser.

In order to determine the loss of retinal sensitivity detectable by oculokinetic perimetry (OKP), we tested 27 eyes of 27 persons with glaucoma and 32 eyes of 32 patients with ocular hypertension with the OKP screener and with a central threshold test on the Humphrey analyser. The threshold at eight locations on the OKP chart between 12.5 degrees and 15 degrees from fixation was compared with the corresponding Humphrey perimetric thresholds. Seventeen eyes from 17 patients with glaucoma failed the OKP screening test by not seeing the target at one or more locations. The mean light sensitivity threshold at points seen on OKP screening was -5.8 dB (SD 4.6 dB) from aged-matched normals (AMN), whereas points missed had a mean threshold -16.1 dB (SD 9.3 dB) from AMN. The sensitivity and specificity with which OKP testing differentiated normal points from abnormal ones in Humphrey testing was 82.5% and 80% respectively, with a threshold criterion of -12 dB from AMN. Ten eyes from 10 patients with glaucomatous defects and all of the ocular hypertensive eyes gave normal responses on the OKP screening test. The glaucomatous eyes that passed were characterized by less severe defects on the Humphrey than those who failed in terms of mean deviation (0.02 < p < 0.05) or corrected pattern standard deviation (0.01 < p < 0.02). Four of the glaucomatous eyes to pass had a nasal step as the primary field defect. None of those to fail failed only on points within 10 degrees of fixation. We suggest further modification of the OKP screening chart to improve its efficiency.

Fixation, Ocular

A population-based evaluation of glaucoma screening: the Baltimore Eye Survey.

The Baltimore Eye Survey was a population-based survey conducted from January 1985 to November 1988 among residents of east Baltimore, Maryland, who were 40 years of age or older. A total of 5,308 black subjects and white subjects received a comprehensive screening examination for glaucoma including tonometry, visual fields, stereoscopic fundus photography, and a detailed medical and ophthalmic history. Based on a definitive examination, a diagnosis of glaucoma of any type was made for 196 persons. Tonometry, cup:disc ratio, and narrowest neuroretinal rim width were evaluated for their ability to correctly classify subjects into diseased or nondiseased states. There were no cutoff values at which these variables provided a reasonable balance of sensitivity and specificity, separately or in combination. Logistic regression models were fit that included demographic and other risk factors. Sensitivities and specificities were calculated for varying cutoff levels on the distribution of predicted probabilities. There was no cutoff for which reasonable sensitivity and specificity were obtained. The authors conclude that the effectiveness of current techniques for glaucoma screening is limited.

Adult

Racial differences in the cause-specific prevalence of blindness in east Baltimore.

BACKGROUND: Bilateral blindness unrelated to simple refractive error is twice as prevalent among blacks as among whites, although the difference narrows among the elderly. The reasons for this race- and age-related pattern are uncertain. METHODS AND RESULTS: A randomly selected, stratified, multistage cluster sample of 2395 blacks and 2913 whites 40 years of age and older in East Baltimore underwent detailed ophthalmic examinations by a single team. We identified 64 subjects who were blind in both eyes. The leading causes of blindness were unoperated senile cataract (accounting for blindness in 27 of the total of 128 eyes), primary open-angle glaucoma (17 eyes), and age-related macular degeneration (16 eyes). Together, these three disorders accounted for 47 percent of all blindness in this sample. Unoperated cataract accounted for 27 percent of all blindness among blacks, among whom it was four times more common than among whites; whites were almost 50 percent more likely than blacks to have undergone cataract extraction before the age of 80 (P less than 0.002). Primary open-angle glaucoma accounted for 19 percent of all blindness among blacks; it was six times as frequent among blacks as among whites and began 10 years earlier, on average. By contrast, age-related macular degeneration resulting in blindness was limited to whites, among whom it was the leading cause of blindness (prevalence, 2.7 per 1000; 95 percent confidence interval, 1.2 to 5.4); it affected 3 percent of all white subjects 80 years of age or older. CONCLUSIONS: The pattern of blindness in urban Baltimore appears to be different among blacks and whites. Whites are far more likely to have age-related macular degeneration, and blacks to have primary open-angle glaucoma. The high rate of unoperated cataracts among younger blacks and among elderly subjects of both races suggests that health services are underused. Half of all blindness in this urban population is probably preventable or reversible.

Adult

Relationship between intraocular pressure and primary open angle glaucoma among white and black Americans. The Baltimore Eye Survey.

A detailed ocular examination, including perimetry, was conducted on 5308 black and white subjects aged 40 years and older in a population-based prevalence survey in east Baltimore, Md. Repeated, detailed examinations were carried out on selected subjects. Roughly half of all subjects with optic nerve damage from primary open angle glaucoma, regardless of race, were unaware that they had the condition. The average intraocular pressure (IOP) among black patients with glaucoma who were receiving treatment was virtually identical to that in those black patients who were not receiving treatment (median IOP, 20 mm Hg); treated eyes of white patients had a lower IOP than those eyes of white patients who were not receiving treatment (mean [+/- SD] IOP, 18.69 +/- 3.23 mm Hg vs 24.15 +/- 5.23 mm Hg; P less than .001). The risk of glaucomatous optic nerve damage increased with the height of the screening IOP, particularly at levels of 22 to 29 and 30 mm Hg and above (relative rate compared with IOP of 15 mm Hg or lower, 12.8 and 40.1 mm Hg, respectively). More than half of all glaucomatous eyes had a screening IOP below 21 mm Hg, whether these eyes were receiving treatment or not. The IOP in glaucomatous eyes tended to rise on follow-up, in contrast with nonglaucomatous eyes in which the IOP was as likely to rise as to fall. Results confirmed that IOP is an important factor in glaucoma, but did not support the traditional distinction between "normal" and "elevated" pressure, nor its corollaries, "low-tension" glaucoma and "high-tension" glaucoma.

Black People

Larger optic nerve heads have more nerve fibers in normal monkey eyes.

The cup-to-disc ratio and the neural rim area are used to detect glaucoma damage to the optic nerve. Both parameters are dependent on the size of the optic disc and on the number of optic nerve fibers. We compared the size of the disc in fundus photographs with the number of nerve fibers in 25 normal monkey eyes. The number of fibers increased linearly with an increasing disc area. One must know the size of the optic disc to evaluate properly the cup-to-disc ratio or neural rim area.

Animals

Alterations in elastin of the optic nerve head in human and experimental glaucoma.

The optic nerve heads from normal and glaucomatous eyes of humans and monkeys were examined by light and electron microscopy for the presence and distribution of elastin. Elastin densely lined the insertion of the lamina cribrosa into the sclera and was prominent in the laminar beams. The long axis of elastin paralleled that of the collagen fibrils and corresponded to the directions of expected forces on the tissue. In glaucomatous eyes elastin molecules were curled instead of straight and seemed disconnected from the other elements of the connective tissue matrix. Laminar beams stretch and reorganise their substructure during glaucomatous atrophy, probably leading to changed compliance. Differences in elastin function may have a part in susceptibility to glaucomatous injury.

Aged

Quantitative study of collagen and elastin of the optic nerve head and sclera in human and experimental monkey glaucoma.

Quantitative studies of collagen density and fibril size distribution as well as elastin density were carried out in the optic nerve head and sclera of human and experimental monkey glaucoma eyes. The collagen fibrils of the normal lamina cribrosa are smaller and more uniform in size than those of the sclera. This feature may be an adaptation to maximize either elasticity or resistance to mechanical stress. In glaucomatous nerve heads, there is a major disruption of the structure of the lamina cribrosa beam structure, including a decrease in collagen density. The peripapillary sclera undergoes similar collagen density changes to those in the nerve head in human glaucoma eyes. Elastin fiber density is unchanged in the glaucomatous nerve heads that we studied.

Aged

In vitro release of hydrophobic drugs from polyanhydride disks.

We have evaluated the feasibility of using polyanhydride disks containing hydrophobic antiproliferative agents for controlled drug release after glaucoma filtration surgery. Taxol and VP-16 were the most potent inhibitors of fibroblast proliferation tested, with ID50s of 3 ng/mL and 200 ng/mL, respectively. In vitro release of taxol occurred at concentrations exceeding its ID50 for at least 100 days; VP-16 was released for 31 days. The media into which the drugs were released were able to inhibit fibroblast proliferation in vitro, indicating that the bioactivity of the drugs withstood incorporation into, and release from, the polyanhydride. Polyanhydride disks containing taxol and VP-16 merit testing in animal models of glaucoma filtration surgery.

Alkaloids

Selective effects of experimental glaucoma on axonal transport by retinal ganglion cells to the dorsal lateral geniculate nucleus.

Rapid-phase axonal transport to the dorsal lateral geniculate nucleus (dLGN) was determined autoradiographically in seven macaque monkey eyes with chronic intraocular pressure (IOP) elevation, in four eyes with an acute IOP elevation, and in three eyes with normal IOP. The monkeys with chronic IOP elevation showed a greater decrease in radioactive labeling of the magnocellular layers of the dLGN than the parvocellular layers by qualitative examination. Grain counts in selected specimens confirmed that transport to the magnocellular layers was less than to the parvocellular layers in monkeys with chronic IOP elevation. This selectivity was present in mildly damaged specimens and increased with greater ganglion cell loss. In monkeys with acute IOP elevation, qualitative evaluation suggested no consistent difference in transport among the dLGN layers; one animal in this group had less transport to the parvocellular than to the magnocellular layers by grain counts. Starting in early stages of the disease, chronic experimental glaucoma causes preferential damage to the ganglion cells that project to the magnocellular layers of the dLGN.

Animals

Transscleral cyclophotocoagulation of human autopsy and monkey eyes.

We studied the effect of uveal pigmentation on contact Nd:YAG transscleral cyclophotocoagulation in 36 human autopsy and eight cynomolgus monkey eyes. Ten autopsy eyes from black individuals required less energy to create a lesion than 23 eyes from whites. The mean lesion diameter at the posterior pars plicata was similar in all these eyes; however, the mean energy required was 4.4 J in the black and 6.4 J in the white eyes. Transscleral cyclophotocoagulation lowered intraocular pressure (IOP) in four monkey eyes with elevated IOP, but did not in four other eyes without elevated IOP. Treatment over conjunctival pigmentation burned the conjunctiva, even at the lowest energy tested (3.5 J). Contrary to other investigators' findings, transmission electron microscopy showed at least short-term loss of scleral architecture in both the human autopsy and monkey eyes.

Animals

Blockade of rapid axonal transport. Effect of intraocular pressure elevation in primate optic nerve.

After acute intraocular pressure (IOP) elevation, an induced disturbance of rapid axonal transport at the optic nerve head began within three hours at the IOP levels tested. The accumulation of radioactive label at the scleral lamina cribrosa increased with time of IOP elevation. There was a 60% decrease in the amount of transported material in the optic nerve, tract, and lateral geniculate body (LGN). Detailed analysis suggests that this decrease is not due to a simple slowdown of transport, but results from a total block of rapid transport in some axons, with no impairment in other axons. This total blockade of rapid transport by elevated IOP in involved axons differs from the apparent slowdown of transport in experimental papilledema, and the difference may explain the response of ganglion cells to the two conditions.

Animals