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Biomedical subjects

G A Cioffi

Publications and source records attributed to G A Cioffi.

At least 37 records · Page 2Linked to original sources

The Glaucoma Symptom Scale. A brief index of glaucoma-specific symptoms.

OBJECTIVE: To develop a brief symptom survey specific for persons with glaucoma, the Glaucoma Symptom Scale (GSS). DESIGN: Cross-sectional study of symptoms, functional impairment, and vision-targeted health-related quality of life among persons with glaucoma. PATIENTS: A sample of 147 persons with glaucoma among a broad range of treatment categories from 4 tertiary care glaucoma centers and 44 persons without eye disease enrolled from the same 4 centers. MAIN OUTCOME MEASURES: Participants completed a modified version of the Ocular Hypertension Treatment Study 10-item symptom checklist. Participants also completed 2 vision-specific measures, the National Eye Institute Visual Function Questionnaire and the VF-14. Participants underwent a clinical evaluation, including ocular and medical history, dilated ophthalmic examination, and Humphrey 24-2 automated visual field testing. RESULTS: The GSS has 2 underlying domains that demonstrate sufficient internal consistency reliability for between-group comparisons. The GSS discriminates well between persons with and without glaucoma. Additionally, tests of association with clinical markers of glaucoma severity support the clinical validity of the measure and tests of association with established vision-targeted measures provide evidence of construct validity. CONCLUSION: The simplicity, brevity, and psychometric properties of the GSS support its use in clinical practice and research to quantify symptoms in patients with glaucoma and to assist in investigations concerning the effect of glaucoma and treatments.

Cross-Sectional Studies↗

Latanoprost treatment for glaucoma: effects of treating for 1 year and of switching from timolol. United States Latanoprost Study Group.

PURPOSE: To determine the efficacy and safety of latanoprost treatment for 1 year in glaucoma patients, and to evaluate the effects of switching from timolol to latanoprost therapy. METHODS: Latanoprost 0.005% was topically applied once daily without masking for 6 months in 223 patients with elevated intraocular pressure after previous treatment with latanoprost once daily or 0.5% timolol twice daily for 6 months in a multicenter, randomized, double-masked, parallel group study. RESULTS: Compared with baseline values before treatment, a significant (P < .0001) diurnal reduction in intraocular pressure of 6 to 8 mm Hg was maintained with minimal fluctuation for the duration of treatment. When treatment was switched from timolol to latanoprost, intraocular pressure was reduced by 1.5 +/- 0.3 mm Hg (mean +/- SEM; 8% change in intraocular pressure; 31% of the intraocular pressure reduction produced by timolol; P < .001) compared with the change in intraocular pressure in patients remaining on latanoprost therapy. Of the patients initially enrolled, 95% successfully completed treatment. There was a slight overall increase in conjunctival hyperemia in patients who switched from timolol to latanoprost, but no change in those who continued latanoprost. The timolol-induced reduction of resting heart rate returned to baseline levels after switching to latanoprost. Of the 247 patients treated with latanoprost during the masked and/or open-label studies, 12 (5%) demonstrated a definite (n = 4) or possible (n = 8) increase in iris pigmentation. CONCLUSIONS: Latanoprost is a well-tolerated ocular hypotensive agent that appears to be more effective than timolol in reducing intraocular pressure. The increase in iris pigmentation appears to be harmless but requires further investigation.

Adult↗

The vascular pattern of the optic nerve and its potential relevance in glaucoma.

Evidence that vascular factors contribute to the pathogenesis and development of glaucomatous optic neuropathy continues to accumulate. A higher than expected prevalence of systemic vascular disorders in individuals with glaucoma has been documented. New sophisticated in vivo analysis techniques, such as ultrasound color Doppler imaging, suggest that decreased blood flow velocity and increased vascular resistance are present in the vessels serving the optic nerve of human subjects with glaucoma, implying the presence of either organic or functional vascular disorders in these individuals. Recognizing that different analysis techniques have led to conflicting observations, experimental models have been developed to provide an additional tool with which to interpret the effects of compromised optic nerve perfusion.

Animals↗

Influence of glaucomatous visual field loss on health-related quality of life.

We examined the influence of glaucomatous visual field defects on vision-targeted and generic health-related quality of life. Vision-targeted and generic health status were assessed across 5 glaucoma treatment categories and a normal reference group from 5 tertiary care ophthalmology practices during regularly scheduled eye care visits. The sample consisted of 147 patients who were members of specific glaucoma treatment categories and 44 reference group patients. For patients with glaucoma, eligibility included a diagnosis of glaucoma at least 1 year prior to enrollment and no evidence of other eye disease. Participants completed 2 vision-targeted surveys, the National Eye Institute Visual Functioning Questionnaire and the VF-14, and a generic health-related quality of life measure, the Medical Outcomes Study 36-Item Short Form. Data from automated perimetry (Humphrey Field Analyzer 24-2, Humphrey Instruments, San Leandro, Calif) were used to generate Advanced Glaucoma Intervention Study scores for all participants. The Medical Outcomes Study 36-Item Short Form scores from glaucoma and reference group participants collected on a random half of the sample were similar. However, comparisons of the vision-targeted surveys demonstrated significant mean differences on 7 of 11 National Eye Institute Visual Functioning Questionnaire scales, and a trend toward significant differences for the VF-14 (P < .07 by linear regression). Greater visual field defects in the better eye were significantly associated with poorer National Eye Institute Visual Functioning Questionnaire scores (P < .05), as well as with worse VF-14 scores. These findings were most dramatic for patients with the most severe field loss in the better eye. Vision-targeted questionnaires were more sensitive than a generic health-related quality of life measure to differences between glaucoma and normal reference participants. Our findings indicate that self-reports of vision-targeted health-related quality of life are sensitive to visual field loss and may be useful in tandem with the clinical examination to fully understand outcomes of treatment for glaucoma.

Adult↗

A multicenter comparison study of the Humphrey Field Analyzer I and the Humphrey Field Analyzer II.

PURPOSE: The purpose of the study is to determine the comparability of the 30-2 full-threshold program in the original Humphrey Field Analyzer (HFA) I to the same test procedure in the new Humphrey Field Analyzer II. METHODS: At each of five clinical centers, one eye of patients with ocular hypertension and normal visual fields, patients with early glaucomatous visual field loss, and patients with more advanced visual field loss were tested with the two instruments plus a retest on a separate HFA I. All participants had undergone at least one prior visual field examination. To minimize the influence of any residual learning or fatigue effects, the order of testing for the three visual field examinations was counterbalanced across subjects. A total of 250 patients were tested (81 patients with ocular hypertension, 81 patients with early glaucomatous visual field loss, and 88 patients with more advanced glaucomatous visual field loss). RESULTS: No statistically significant differences were observed between thresholds, visual field indices, or reliability indices obtained with the HFA I and the HFA II. The small differences between the two instruments were equivalent to the variation observed for test-retest measures using only the HFA I. These results were consistent across the range of visual field characteristics shown by the ocular hypertensive, early glaucoma, and moderate glaucoma patient groups. CONCLUSIONS: The authors' results indicate that there are no differences in the visual field results obtained with the HFA I and the HFA II. These findings suggest that with careful attention to test protocols, the HFA I and HFA II may be used interchangeably to observe patients, even within the context of multicenter clinical trials.

False Negative Reactions↗

Sources of variability of topometric data with a scanning laser ophthalmoscope.

OBJECTIVE: To determine in a two-part study whether misalignment between the patient and the laser scanner is a major source of variability with the Heidelberg Retina Tomograph (Heidelberg [Germany] Engineering). METHODS: Three topographic images of the right optic nerve were acquired with the Heidelberg Retina Tomograph in eight patients with glaucoma. The correlations between average cup volume, variability of cup volume estimates, and direction of imaging were evaluated. Furthermore, the correlations between average rim volume, variability of rim volume estimates, and direction of imaging were evaluated. Next, the optic nerve cup volume and rim volume estimates of a rabbit's left eye were compared between three series of five topographic images acquired from three slightly different directions. RESULTS: Average cup volume, variability of cup volume estimates, and variability in the direction of imaging correlated significantly among the patients with glaucoma (multiple R2 = .95; P < .001). Average rim volume, variability of rim volume estimates, variability in the direction of imaging, and variability in the mean height of the contour line also correlated significantly (multiple R2 = .88; P = .03). In the rabbit eye, the cup volume and the rim volume differed significantly among the three image series (analysis of variance, P < .001 and P = .04, respectively). CONCLUSION: Misalignment between the patient and the laser scanner may account for significant variability with the Heidelberg Retina Tomograph.

Animals↗

Measurement of optic nerve blood flow with nonradioactive colored microspheres in rabbits.

The objective of this study was to establish a nonradioactive technique to accurately assess blood flow in a small tissue such as the anterior optic nerve. Colored microspheres, 10.2 +/- 0.23 microns in diameter, were injected into the left atrium in each of 17 anesthetized rabbits. The rabbits were divided into four groups injected, respectively, with 5, 10, 50, or 100 million microspheres. Microsphere quantification in the tissue was performed after postmortem dissection and alkaline corrosion of the anterior optic nerve. Blood flow was evaluated by means of reference sample comparison method. While the relative interocular difference (range, 15.3-162.8%) was not significantly different between the rabbits injected with 5, 10, or 50 million microspheres (Kruskal-Wallis test, P = 0.11), injection with 100 million microspheres yielded a significantly lower relative interocular differences (range 2.3-12.8%) compared to the other three groups (Kruskal-Wallis test, P = 0.0048). In addition, reproducibility of microsphere counts was evaluated by ranking the difference between right and left optic nerve in percentage of the average number of microspheres per milligram of tissue in both optic nerves. The correlation between the relative interocular difference (range, 2.3-162.8%) and the average number of microspheres per milligram of tissue (1.2-78.7 microspheres/mg optic nerve tissue) was statistically significant (Spearman R, -0.90; P < 0.0001). The interocular variability in microsphere counts and interocular difference in intraocular pressure did not correlate (Spearman R, 0.33; P = 0.20). The rabbits injected with 100 million microspheres showed the highest average number of microspheres (range, 31.8-78.7 microspheres/mg optic nerve tissue). The optic nerve blood flow ranged between 0.14 and 0.24 microliters/mg/min among the rabbits injected with 100 million microspheres. The present experimental technique of optic nerve blood flow measurement is relatively inexpensive, highly reproducible, and obviates disposal of radioactive materials.

Animals↗

In vivo detection of perineural circular arterial anastomosis (circle of Zinn-Haller) in a patient with large peripapillary chorioretinal atrophy.

PURPOSE: In vivo visualization of perineural circular arterial anastomosis (circle of Zinn-Haller) has been considered impossible because of the arterial circle's location in the sclera. We investigated whether the circle of Zinn-Haller could be detected in a glaucoma patient who had a large area of temporal peripapillary chorioretinal atrophy. METHODS: We performed both scanning laser Doppler flowmetry and indocyanine green angiography with a scanning laser ophthalmoscope in the same patient. RESULTS: In the area of peripapillary atrophy, a circumferential vascular loop consistent with a portion of the circle of Zinn-Haller could be detected by the two imaging methods. CONCLUSION: The circle of Zinn-Haller can be visualized in vivo because of the peripapillary atrophy.

Arteries↗

Optic nerve vasomotor effects of topical apraclonidine hydrochloride.

AIMS: To examine, in vivo, the anterior optic nerve vasomotor effects of chronic apraclonidine hydrochloride in rabbits. METHODS: After local treatment in one randomly chosen eye with apraclonidine hydrochloride 0.5% over 21 days, the microvasculature of the optic nerve was examined in five rabbits using an intraluminal microvascular corrosion casting technique. The investigators were masked as to which eye was treated. The vasoconstriction near the branching point of arterioles supplying the optic nerve was calculated as a percentage of the downstream vessel calibre. An average constriction was calculated and compared between the treated and the contralateral, untreated, eyes by means of a two tailed t test for paired variables. Constriction values of a total of 72 arterioles supplying the optic nerve were obtained for the five rabbits. RESULTS: The average constriction in the treated and the control eyes was comparable (p = 0.96). CONCLUSION: Chronic administration of apraclonidine hydrochloride 0.5% produces no observable optic nerve vasomotor effects in the rabbit eye.

Administration, Topical↗

An endothelin-1 induced model of optic nerve ischemia in the rabbit.

PURPOSE: To evaluate blood flow reduction and topographic optic nerve changes after the local administration of endothelin-1 in vivo, delivered to the perineural region of the anterior optic nerve in the rabbit. METHODS: Endothelin-1 (five rabbits) in a dosage of 0.1 microgram/day or balanced salt solution (two rabbits) was delivered to the perineural region of the anterior optic nerve with osmotically driven minipumps. Optic nerve blood flow was determined by the colored microspheres technique after 14 days of local endothelin-1 or balanced salt solution administration to the microvasculature of the optic nerve. In addition, optic nerve blood flow was determined in two rabbits that had no minipump implants. The morphologic changes induced by reduction of blood flow were assessed in five additional rabbits implanted with osmotically driven minipumps containing endothelin-1 (0.1 microgram/day). These rabbits were observed for 8 weeks, and the morphologic optic nerve changes were monitored with a confocal scanning laser ophthalmoscope. RESULTS: Independent of intraocular pressure, endothelin-1 induced a decrease in blood flow of approximately 38% in the experimental eye, compared to the decrease induced by balanced salt solution or to the decrease in rabbits without minipumps (analysis of covariance, P = 0.0092). Multivariate statistical analysis showed a significant change in topometric parameters (cup area, cup depth, rim volume) obtained with a confocal scanning laser ophthalmoscope, indicating an increase in optic nerve cupping and a decrease of the perineural rim volume in the experimental eyes (P = 0.017). CONCLUSIONS: The current results suggest that morphologic optic nerve alterations can be induced experimentally in the rabbit model after ischemia produced by the local administration of endothelin-1 to the perineural region of the anterior optic nerve.

Animals↗

An endothelin-1-induced model of chronic optic nerve ischemia in rhesus monkeys.

PURPOSE: The purpose of this study was to evaluate flow reduction to the optic nerve after chronic administration of endothelin-1 in primates. MATERIALS AND METHODS: Endothelin-1 (three rhesus monkeys), in a dosage of 0.1 microgram/day, or balanced salt solution (three rhesus monkeys) was delivered to the perineural region of the anterior optic nerve via osmotically driven minipumps. Optic nerve blood flow was determined by means of a colored microspheres technique after 7 days of local endothelin-1 or balanced salt solution administration. The effect of endothelin-1 on optic nerve blood flow was analyzed by analysis of convariance (ANCOVA) in a 2 (between groups: endothelin-1, balanced salt solution) x 2 (within subject: blood flow minipump optic nerve, blood flow controls) design, with intraocular pressure as a changing covariate. RESULTS: The decrease of optic nerve blood flow in the endothelin-1 eyes was significant compared to the balanced salt solution eyes (ANCOVA p = 0.015). Among the monkeys implanted with endothelin-1 minipumps, the decrease in optic nerve blood flow in the experimental eye compared to the contralateral eye (mean +/- SD 35.7 +/- 9.1%) was significant (p = 0.01), while that among the monkeys implanted with balanced salt solution minipumps (mean +/- SD 0.7 +/- 5.5%) was not (p = 0.73). CONCLUSIONS: This new primate model of chronic optic nerve ischemia may represent a method to evaluate experimentally the implication of a local hemodynamic perturbation in various optic neuropathies.

Animals↗

Optic nerve vasomotor effects of topical beta-adrenergic antagonists in rabbits.

PURPOSE: To examine the anterior optic nerve vasomotor effects of nonselective and relatively beta-1-selective beta-adrenergic antagonists in rabbits, because different influences on optic nerve blood flow with these medications have been suggested. METHODS: After topical therapy for 30 days with either timolol maleate 0.5% (six rabbits), betaxolol hydrochloride 0.5% (six rabbits), or placebo (two rabbits), the microvasculature of the optic nerve was examined with an intraluminal microvascular corrosion casting technique. The investigators were masked to both the medication group and the treated eye. The constriction, in percent of the downstream vessel caliber, was measured at the vascular branching point of arterioles supplying the anterior optic nerve. An average constriction was calculated and compared between the medication groups and between the treated and the contralateral, untreated eyes. RESULTS: Constriction values from a total of 218 arterioles supplying the anterior optic nerve were obtained for the 14 rabbits. The means of the average constriction on the treated side were comparable between the groups treated with timolol maleate, betaxolol hydrochloride, and placebo (one-way analysis of variance, P = .64), as well as between the treated and untreated eyes (two-tailed t-test for paired variables, P = .68 for timolol maleate and P = .42 for betaxolol hydrochloride). The statistical power to find a difference of 5% or more average constriction was at least 90%. CONCLUSIONS: Both relatively selective and nonselective beta-adrenergic antagonists produce no observable optic nerve vasomotor effects in the rabbit eye.

Administration, Topical↗

Microvasculature of the human optic nerve.

PURPOSE: Methyl methacrylate vascular corrosion casting techniques were used to examine the normal anterior optic nerve microvasculature in 18 human eye bank eyes. METHODS: Selective cannulation of the central retinal artery, the short posterior ciliary arteries, or both, allowed the methyl methacrylate to be injected into the anterior optic nerve circulation. Preflushing with tissue plasminogen activator greatly enhanced the filling of the fine microvasculature by dissolving the intraluminal clots. RESULTS: The superficial nerve fiber layer of the optic nerve received its primary blood supply from the central retinal artery. In 11 of 13 eyes injected with methyl methacrylate through the short posterior ciliary arteries, there was a perineural, circular arterial anastomosis (circle of Zinn-Haller) at the scleral level. Branches from this circle penetrated the optic nerve to supply the prelaminar and laminar regions and the peripapillary choroid. In the two eyes without this arterial circle, direct branches from the short posterior ciliary arteries supplied the anterior optic nerve. The venous drainage of the anterior optic nerve was almost entirely through the central retinal vein and its tributaries. CONCLUSIONS: This study demonstrates that the main arterial vascular supply to the anterior optic nerve is from the short posterior ciliary arteries. The contribution of the peripapillary choroid to the anterior optic nerve is minimal in comparison to the direct contribution from the short posterior ciliary arteries.

Arteries↗

Foveal adaptation abnormalities in early glaucoma.

Foveal sensitivities were measured after onset of adapting background fields for each of the following four groups of subjects aged 40-70 years: (1) low-tension glaucoma subjects with minimal field loss in the test eye, (2) primary open-angle glaucoma subjects with minimal field loss in the test eye, (3) normal control subjects, and (4) subjects originally enrolled as control subjects but subsequently found, on the basis of masked clinical evaluation, to be suspect for glaucoma despite ostensibly normal intraocular pressures. We found that the desensitization of a short-wavelength-sensitive-cone-mediated response after onset of a 580-nm background field was diminished from that of normal observers for low-tension glaucoma subjects but not for primary open-angle glaucoma subjects. The desensitization was also diminished for a glaucoma-suspect subjects aged 60-70 years. In contrast, the flicker sensitivity instabilities that persisted after onset of a long-wavelength background field for the majority of subjects with primary open-angle glaucoma [J. Glaucoma Suppl. 3, S19 (1994)] occurred only infrequently among the other subject groups. These results imply that glaucoma often involves the fovea, probably by affecting retinal subtractive adaptation processes, although with different consequences for different types of glaucoma. The results also suggest that undiagnosed low-tension glaucoma may not be rare in the general aging population.

Adaptation, Ocular↗