Tonometry and corneal thickness.
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Adolescent↗
Biomedical subjects
R F Brubaker
Publications and source records attributed to R F Brubaker.
Measurement of aqueous humor flow by fluorophotometry in the presence of a dilated pupil.
PURPOSE: To determine by means of fluorophotometry whether pharmacologic dilation of the pupil can interfere with the measurement of aqueous flow. METHODS: Ten normal human volunteers underwent dilation with tropicamide, phenylephrine, and a combination of the two drugs. Before and after dilation, the rate of aqueous flow was measured by the rate of disappearance of fluorescein from the cornea and the anterior chamber. RESULTS: Dilation of the pupil with tropicamide alone had no effect on the rate of clearance of fluorescein. Dilation with phenylephrine increased the rate of clearance of fluorescein by 40% and caused a small increase in the variability among subjects. Dilation with a combination of tropicamide and phenylephrine caused clearance of fluorescein at more than double the normal rate and a marked increase in variability among subjects. CONCLUSIONS: When the pupil is dilated sufficiently to permit mixing of aqueous humor in the posterior and anterior chambers, fluorescein can leave the system by a posterior route, and its rate of clearance may not be an accurate measure of the net rate of aqueous humor flow through the anterior chamber.
Adult↗
Additive effect of dorzolamide on aqueous humor flow in patients receiving long-term treatment with timolol.
OBJECTIVE: To determine the additive effect on aqueous humor flow of short-term dorzolamide treatment in patients with glaucoma receiving long-term treatment with timolol. SUBJECTS AND METHODS: Thirty-nine patients with glaucoma, 19 at Mayo Clinic, Rochester, Minn, and 20 at the University of Uppsala, Uppsala, Sweden, who had been receiving timolol treatment in both eyes for at least 1 year were studied. Aqueous flow was measured with fluorophotometry and intraocular pressure with tonometry. The effect of dorzolamide was compared with placebo when added to the long-term treatment regimen with timolol. RESULTS: Dorzolamide reduced aqueous humor flow by 24% +/- 11% (mean +/- SD). The intraocular pressure as compared with placebo in the US cohort was reduced by 10% +/- 6% and in the Swedish cohort by 18% +/- 9%. CONCLUSIONS: Dorzolamide, a carbonic anhydrase inhibitor, has additive effects as an ocular hypotensive agent with timolol, a beta-adrenergic antagonist, even though both drugs are suppressors of aqueous humor flow. Dorzolamide's effect on flow in these patients is the same as reported previously in normal subjects who are not taking a beta-adrenergic antagonist.
Adrenergic beta-Antagonists↗
Comparison of the efficacy of apraclonidine and brimonidine as aqueous suppressants in humans.
OBJECTIVE: To measure and compare the effect of apraclonidine hydrochloride and brimonidine tartrate on the rate of aqueous humor flow in human subjects. SUBJECTS AND METHODS: Forty normal human subjects were given apraclonidine or brimonidine by topical instillation. Aqueous humor flow was measured by the rate of disappearance of topically applied fluorescein. Intraocular pressure was measured by applanation tonometry. RESULTS: Apraclonidine suppressed aqueous humor flow between 39% and 44% and lowered intraocular pressure between 20% and 23%. Brimonidine suppressed aqueous humor flow between 44% and 48% and lowered intraocular pressure between 19% and 22%. CONCLUSION: No statistically significant differences were found between the effects of the 2 drugs on aqueous humor dynamics in normal subjects.
Adrenergic alpha-Agonists↗
Combined effect of dorzolamide and latanoprost on the rate of aqueous humor flow.
PURPOSE: To determine whether latanoprost, an ocular hypotensive agent believed to enhance uveoscleral outflow of aqueous humor, augments the aqueous-suppressing effect of dorzolamide, a topical carbonic anhydrase inhibitor. METHODS: Twenty-four normal subjects underwent measurement of aqueous humor flow by fluorophotometry to determine the flow with placebo, with dorzolamide, and with a combination of dorzolamide and latanoprost. RESULTS: The flow of aqueous humor was suppressed 13% by dorzolamide but not by latanoprost. Latanoprost did not augment the effect of dorzolamide on aqueous humor flow; latanoprost and dorzolamide had additive ocular hypotensive effects. CONCLUSIONS: The uveoscleral flow effect of latanoprost does not improve the aqueous-suppressing effect of dorzolamide, but the two drugs have additive ocular hypotensive effects.
Adult↗
Long-term outcome of patients who undergo tonometry as part of a general physical examination.
OBJECTIVE: To determine the value of including tonometry as part of a general physical examination. MATERIAL AND METHODS: Between Feb. 14, 1977, and Dec. 31, 1980, 849 residents of Rochester, Minnesota, underwent measurement of intraocular pressure by trained ophthalmic technicians at the request of a nonophthalmologist physician as part of a general physical examination. In 1995 and 1996, these cases were reviewed to determine how many patients in this study cohort had subsequently been diagnosed as having glaucoma. The outcome was derived from the examination of medical records and from the responses to mailed questionnaires and telephone interviews with study patients and their physicians. RESULTS: In patients whose intraocular pressures were less than 16 mmHg at baseline, the risk of being diagnosed as having glaucoma within 10 years was 1% (95% confidence interval [CI], 0 to 2%) and within 15 years was 2% (95% CI, 0 to 4%). In patients whose pressure in the higher-pressure eye was 16 to 21 mmHg at baseline, the risk of having glaucoma in 10 years was 3% (95% CI, 2 to 5%) and in 15 years was 5% (95% CI, 3 to 7%). Twenty-four patients were found at baseline to have an intraocular pressure of 22 mmHg or higher in at least one eye or a difference of 5 mmHg or more between the two eyes. In this group, the risk of having glaucoma in 10 years was 17% (95% CI, 0 to 31%) and in 15 years was 26% (95% CI, 6 to 43%). CONCLUSION: When included as part of a general physical examination of older persons, tonometry and a few simple questions provide information that can be used to help the clinician determine the advisability of more detailed ophthalmic examinations.
Adult↗
The effect of dorzolamide on aqueous humor dynamics in normal human subjects during sleep.
OBJECTIVE: The purpose of the study was to measure the effect of the topical carbonic anhydrase inhibitor, 2% dorzolamide hydrochloride, on the rate of aqueous humor flow in sleeping humans. DESIGN: A randomized, double-masked, placebo-controlled study. PARTICIPANTS: Twenty-five normal human subjects. INTERVENTION: Topical instillation of 2% dorzolamide hydrochloride versus topical placebo. MAIN OUTCOME MEASURES: Rate of aqueous humor flow in sleeping humans and intraocular pressure immediately after awakening from sleep. RESULTS: The rate of flow in sleeping subjects at night (12 AM to 6 AM) was 1.28 +/- 0.30 microliters/min (mean +/- standard deviation; n = 25) in placebo-treated eyes, whereas the nighttime flow in dorzolamide-treated eyes was 1.17 +/- 0.38 microliters/min (P = < 0.001), resulting in a nighttime reduction of 9% (P = 0.032). In contrast, the daytime (8 AM to 4 PM) rate of flow in ambulatory subjects was 2.97 +/- 0.64 microliters/min in placebo-treated eyes and 2.60 +/- 0.63 microliters/min (P = 0.032) in dorzolamide-treated eyes, resulting in a daytime reduction of 13% (P = < 0.001). CONCLUSIONS: Topically administered dorzolamide hydrochloride is effective for reducing the rate of aqueous humor flow in normal human eyes during the day and at night during sleep. The efficacy of dorzolamide at these two times is approximately half that of systematically administered acetazolamide.
Administration, Topical↗
Aqueous humor flow in sleeping humans is unaffected by norepinephrine infusion.
PURPOSE: Intravenous administration of the catecholamine epinephrine is known to have a stimulatory effect on aqueous humor flow in sleeping human subjects, an effect that is augmented by plasma corticosteroids. This study was performed to determine whether the closely related catecholamine norepinephrine has a similar effect on aqueous humor flow. METHODS: Twenty normal subjects were studied. Aqueous flow was measured by fluorophotometry. At night during sleep, norepinephrine or placebo was infused intravenously (i.v.) between midnight and 6 AM. The rate of aqueous flow during the norepinephrine infusion was compared with the rate of flow during placebo infusion, with each subject serving as his/her own control. The urinary excretions of epinephrine and norepinephrine were measured at the end of each infusion period. RESULTS: The norepinephrine infusion caused an 8% increase in systolic blood pressure (P < 0.001), a 15% increase in diastolic blood pressure (P < 0.001), and a 9% decrease in heart rate (P=0.003) compared with the placebo. The rate of aqueous humor flow during sleep from 12 AM to 6 AM was unchanged by norepinephrine. The rate was 1.27+/-0.31 microl/min (mean+/-SD) during i.v. infusion of placebo and 1.30+/-0.27 microl/min during infusion of norepinephrine (P=0.63). CONCLUSIONS: An infusion of norepinephrine during sleep that causes measurable changes in cardiovascular parameters has no measurable effects on the rate of aqueous humor flow. The lack of a measurable effect of a norepinephrine infusion contrasts to the stimulatory effect of an epinephrine infusion.
Adult↗
Measuring oxygen tension in the anterior chamber of rabbits.
PURPOSE: Measuring the concentration of oxygen in the aqueous humor without penetrating the eye would provide a new dimension in understanding aqueous humor and corneal dynamics. In this study a preinvasive method was developed for determining the cameral oxygen concentration in anesthetized rabbits by measuring the excited-state lifetime of a phosphorescent dye. METHODS: A scanning ocular fluorometer was designed to excite phosphorescence with a brief flash of light and to measure the decay of luminescence for as long as 1000 microsec after excitation. The measurement window was scanned through the depth of the anterior chamber or fixed at the mid-anterior chamber. A depot of the phosphorescent dye Pd-uroporphyrin was injected into the vitreous of eight pigmented rabbits, and within a few days the dye was measurable in the anterior chamber. The excited-state lifetime of this dye is inversely correlated to oxygen concentration and was calibrated by measuring the lifetime of dye in cuvettes equilibrated with oxygen-nitrogen mixtures. Oxygen tensions were determined from lifetimes measured in the open eye, under a polymethylmethacrylate (PMMA) contact lens, under two oxygen-permeable contact lenses, and immediately after lid closure. RESULTS: Oxygen tension in the mid-anterior chamber before placing a PMMA contact lens was 23 +/- 3 mm Hg (mean +/- SD; n = 6). After 20 minutes of PMMA lens wear, oxygen tension decreased to 4 +/- 2 mm Hg. When the focal diamond was scanned through the anterior chamber, oxygen tension was 24 +/- 5 mm Hg near the corneal endothelium and decreased to 17 +/- 8 mm Hg near the crystalline lens. Under the PMMA contact lens this gradient reversed: Oxygen tensions near the endothelium and lens were 3 +/- 2 mm Hg and 6 +/- 2 mm Hg, respectively. Lid closure for 10 minutes or longer decreased the mid-anterior chamber oxygen tension from 21 +/- 2 mm Hg (n = 19 measurements from seven animals) to 10 +/- 3 mm Hg (n = 15 measurements from five animals). CONCLUSIONS: Measuring excited-state lifetime of phosphorescent dyes in the anterior chamber provides a useful method for determining oxygen concentration in vivo, without penetrating the eye. Cameral oxygen tension under PMMA contact lenses are significantly lower than in the uncovered eye. The profile of oxygen tension through the anterior chamber suggests that oxygen is supplied transcorneally to the aqueous humor.
Animals↗
Response of the pupil to tropicamide is not a reliable test for Alzheimer disease.
OBJECTIVE: To confirm the putative hypersensitivity of the pupil to a weak mydriatic in persons with Alzheimer dementia. DESIGN: Twenty patients with Alzheimer dementia and 20 control subjects were examined. Automated binocular infrared pupillography was performed in the dark after instillation of 0.01% tropicamide or placebo. Ocular penetration of eye drops was assessed simultaneously using 2% fluorescein sodium as a tracer. SETTING: Rochester, Minn. SUBJECTS: Twenty patients and 20 cognitively normal control subjects from the Alzheimer's Disease Patient Registry of the Mayo Clinic, Rochester, Minn. MAIN OUTCOME MEASURE: Percent change in the diameter of the pupil following topical ocular instillation of a diluted concentration of the mydriatic drug tropicamide and penetration of topically applied fluorescein into the aqueous humor. RESULTS: No statistically significant difference was found between patients with Alzheimer disease and control subjects in either the mydriatic response of the pupil or in the rate of penetration of topically applied fluorescein. CONCLUSION: No evidence of pupillary hypersensitivity to an anticholinergic mydriatic drug was found in patients with Alzheimer disease or any evidence that this putative hypersensitivity could be used as an early, simple diagnostic test for Alzheimer disease.
Aged↗
Comparison of dorzolamide and acetazolamide as suppressors of aqueous humor flow in humans.
OBJECTIVE: To compare the efficacy of topical 2% dorzolamide hydrochloride (Trusopt) as a suppressor of aqueous humor flow in the human eye with the efficacy of systemically administered acetazolamide (Diamox). DESIGN: A randomized, double-masked, placebo-controlled study of 40 human subjects in 2 academic centers. The effect of dorzolamide on aqueous humor flow was compared with that of acetazolamide as measured by the rate of clearance of topically applied fluorescein. RESULTS: Acetazolamide reduced aqueous flow from 3.18 +/- 0.70 (mean +/- SD) to 2.23 +/- 0.48 microL per minute, a reduction of 30% (P < .001), and dorzolamide reduced the flow to 2.65 +/- 0.64 microL per minute, a reduction of 17% (P < .001). The difference between the effect of acetazolamine and dorzolamide was significant (P < .001). When acetazolamide is added to dorzolamide, the aqueous flow was reduced further to 2.21 +/- 0.47 microL per minute, an additional reduction of 16% (P < .001). When dorzolamide was added to acetazolamide, no additional reduction was observed (P = .73). Similar effects were observed for intraocular pressure. Acetazolamide reduced pressure from 12.5 +/- 2.2 (mean +/- SD) to 10.1 +/- 2.2 mm Hg, a decrease of 19% (P < .001) and dorzolamide reduced it to 10.8 +/- 2.1 mm Hg, or a decrease of 13% (P < .001). The greater effect of acetazolamide than dorzolamide was significant (P = .03). CONCLUSIONS: For reasons that are not known, the topically applied carbonic anhydrase inhibitor 2% dorzolamide hydrochloride is not as effective as systemically administered acetazolamide. Clinicians who prescribe dorzolamide should expect less of an ocular hypotensive effect than that experienced from systemically administered acetazolamide.
Acetazolamide↗
Effects of exogenous prostaglandins on aqueous humor dynamics and blood-aqueous barrier function.
Topical prostaglandins (PGs) are very effective at reducing intraocular pressure (IOP) in a variety of animals and in humans with relatively few side effects. The mechanisms of action of several PGs, their prodrugs and analogues have been studied in rabbits, cats, monkeys and humans. PGF2 alpha and its analogues evaluated in monkeys include PGF2 alpha-tromethamine salt, PGF2 alpha -isopropylester (-IE), S-1033, PhXA34, PhDH100A and latanoprost (PhXA41). Aqueous flow and outflow facility are either increased or remain unchanged by these agents. PGF2 alpha-IE, PHXA34, PhDH100A and latanoprost increase uveoscleral outflow, accounting for most of the IOP reduction. PGA2 in cats increases aqueous flow and outflow facility, but it reduces IOP primarily by stimulating uveoscleral outflow. The PGD2 analogue BW245C is unique in that it is the only PG that decreases aqueous flow. Mechanistic studies in humans have been performed with PGF2 alpha -IE, unoprostone, PhXA34 and latanoprost. In two clinical studies with latanoprost, a significant increase in uveoscleral outflow was found which, as in animals, accounts for most of the IOP reduction. A slight but inconsistent increase in outflow facility may also be involved. The doses tested had minimal effects on the permeability of the blood-aqueous barrier (BAB). In vitro studies of human tissue have been conducted to elucidate the PG effect on outflow facility and uveoscleral outflow. Studies of isolated human anterior segment preparations show that PGE2 increases outflow facility whereas PGF2 alpha has no measurable effect on this parameter. Studies of human ciliary muscle cells in tissue culture indicate that PGs may directly modulate extracellular matrix metabolism, which may be related to the increased uveoscleral drainage. This review summarizes in vitro and in vivo studies of the effects of PGs on aqueous humor dynamics and BAB integrity in humans, cats and monkeys.
Animals↗
Structure and function of the corneal endothelium in diabetes mellitus type I and type II.
OBJECTIVE: To measure and compare corneal endothelial morphologic characteristics and function in subjects with diabetes mellitus types I and II. DESIGN: Forty-nine patients with diabetes mellitus type I and 60 patients with diabetes mellitus type II were recruited from the active practice of the Mayo Clinic, Rochester, Minn. Thirty-one normal subjects, divided by age into two overlapping groups of 20 each, served as controls. Corneal endothelial permeability and corneal autofluorescence were measured by fluorophotometry. Central corneal endothelial photographs were taken with a wide-field specular microscope, which also measured the corneal thickness. RESULTS: Neither the type I nor the type II diabetics differed from their controls in endothelial permeability and endothelial cell density. The type I diabetics had polymegethism, pleomorphism, increased corneal thickness, and increased corneal autofluorescence compared with their controls. Similar measured values were found in the type II diabetics, but they did not differ significantly from those of their age-matched controls. The type II diabetics were older than the type I diabetics, and the older control group showed changes similar to those seen in the diabetics; these changes were presumably associated with aging. The severity of retinopathy was significantly correlated only with corneal autofluorescence. CONCLUSION: The corneas of patients with type I diabetes mellitus exhibit abnormalities in endothelial cell morphologic characteristics and corneal autofluorescence. The changes resemble those that occur with aging in normal subjects, making them difficult to discern as abnormal in type II diabetics, who are usually older. We found no abnormalities in endothelial permeability in either type I or type II diabetics.
Adolescent↗
The effects of sleep on circulating catecholamines and aqueous flow in human subjects.
We measured the rate of aqueous flow and analysed its relation to the time of day, the state of wakefulness and the urinary excretion of catecholamines. Two groups of subjects were studied. One group comprised 20 normal subjects who were studied over two 22-hr periods. During one period, the subjects were permitted to sleep during their customary hours of sleep; during the other, they were not permitted to sleep, but remained active for all 22 hr. The other group comprised ten subjects with obstructive sleep apnea who were studied over a 22-hr period and slept during their customary hours of sleep but without the aid of any respiratory device. Aqueous flow was measured with fluorophotometry. Motion of the wrist was monitored by a seismograph (wrist Actigraph) and served as a surrogate of activity and wakefulness. Urinary catecholamine excretion was measured during different periods of the wake/sleep cycle. Both groups exhibited the normal nocturnal suppression of flow (59% lower compared to morning in the normal group; 56% lower compared to morning in the apneic group). During sleep deprivation, the rate of flow at night in normal subjects was 30% lower than during the morning (P < 0.001) and 60% higher than during sleep (P < 0.001). Lid closure during sleep deprivation had no effect on the results. Aqueous flow correlated with a 'catecholamine index', derived from the combined excretion of epinephrine and norepinephrine. Flow also correlated with an 'activity index', and 'sleep efficiency', indices derived from motion of the wrist. We conclude that the day-night difference of aqueous humor flow as measured by clearance of fluorescein from the human eye is driven partly by a factor that has a circadian rhythm and partly by a factor that depends on the activity of the subject. We hypothesize that these factors are the catecholamines, epinephrine and norepinephrine.
Adult↗
Delayed functional loss in glaucoma. LII Edward Jackson Memorial Lecture.
PURPOSE: This study is a systematic exploration of why some patients with glaucoma continue to lose visual field long after therapeutic normalization of their increased intraocular pressures. METHODS: Three cases of glaucoma are described that had increased intraocular pressures and good initial visual fields. RESULTS: The following four hypotheses are offered to explain delayed functional loss in these patients: (1) A process independent of intraocular pressure is killing ganglion cells. (2) Unmeasured increases of pressure are killing ganglion cells. (3) The ganglion cells have a genetically determined hypersensitivity to intraocular pressure. (4) The ganglion cells have been rendered hypersensitive to intraocular pressure by irreversible damaging effects of previously increased intraocular pressures CONCLUSION: The current state of knowledge does not permit the elimination of any of the four hypotheses. An additional hypothesis is that the final stage of ganglion cell death is mediated by apoptosis. If so, a potential new treatment for glaucoma would be to inhibit the apoptotic pathway.
Adult↗
Combined corticosteroid and catecholamine stimulation of aqueous humor flow.
PURPOSE: Epinephrine is known to stimulate aqueous humor flow in humans. Corticosteroids are known to augment the effect of beta-adrenergic agonists on the ciliary body. This experiment was carried out to determine whether a corticosteroid can increase the stimulatory effect of epinephrine on aqueous humor flow. METHODS: Twenty human volunteers were studied for 24 hours. Hydrocortisone was given orally and epinephrine was given intravenously during sleep while aqueous flow was monitored. Flow was compared with a second 24-hour study when oral and intravenous placebos were given. The sequence of administration was randomized. Subjects and investigators were masked. The flows also were compared with a previously published study in which the same dose of epinephrine was administered without steroid. RESULTS: Epinephrine plus hydrocortisone compared with placebos increased aqueous flow 42% in subjects during sleep. The combination of epinephrine and hydrocortisone was a more potent stimulus to aqueous flow than epinephrine alone, which increased aqueous flow by only 27% (P = 0.045). CONCLUSION: The two major hormones of the adrenal gland work in concert to increase the rate of aqueous humor flow in humans.
Administration, Oral↗
Measurement of transmission of ultraviolet and visible light in the living rabbit cornea.
Corneal transmittance in pigmented rabbits was measured at ultraviolet and visible wavelengths from the ratio of fluorescence of dyes in the anterior chamber to fluorescence of the same dyes in a quartz cuvette. Aqueous humor was drained through a limbal incision and the anterior chamber was reformed with a mixture of a viscoelastic material and a fluorophore (fluorescein, O-methyl pyranine, or sulforhodamine B). Excitation spectra, emission spectra, or both were measured in the anterior chamber with a new scanning ocular fluorophotometer, at wavelengths between 250 nm and 700 nm. Fluorescence spectra were also measured from the same fluorophore in a quartz cuvette. External transmittance of the cornea was calculated at each wavelength from the ratio of fluorescence in the anterior chamber to fluorescence in the cuvette. Transmittance was 93% +/- 1.4% (mean +/- SD, n = 8 rabbits) at 500 nm and was 89% to 93% between 370 nm and 500 nm. Transmittance decreased to 82% +/- 5.7% at 350 nm, to 50% +/- 5.9% at 310 nm, and to less than 2% at 290 nm. Between 370 nm and 500 nm, the wavelength range most frequently used in fluorophotometry, average transmittance varied by less than 5%. These results suggest that fluorescence measured at two or more wavelengths within this spectrum needs little if any correction for differential attenuation by the cornea. At wavelengths shorter than 370nm, measurements should be corrected. This technique provides a simple and minimally invasive means of studying visible and ultraviolet transparency of the cornea in the living eye.
Animals↗