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Biomedical subjects

R F Brubaker

Publications and source records attributed to R F Brubaker.

At least 91 records · Page 5Linked to original sources

Endothelial function and aqueous humor flow rate in patients with Fuchs' dystrophy.

Using a two-dimensional scanning fluorophotometer, we studied 50 subjects with symmetric ocular involvement of Fuchs' dystrophy without epithelial edema. Twenty-six subjects with confluent or nearly confluent cornea gutata with increased corneal thickness and 24 subjects with mild to moderate cornea guttata with normal corneal thickness were compared to normal control subjects. There were no statistically significant differences in endothelial permeability between the three groups. Corneal thickness was significantly increased in the subjects with confluent to nearly confluent guttae, however. These results suggest that endothelial pump function may be affected in subjects with advanced cornea guttata with stromal edema.

Aqueous Humor↗

Traumatic hyphema in a defined population.

From 1960 through 1984, traumatic hyphema was diagnosed in 248 residents (204 males and 44 females) of Olmsted County, Minnesota. The mean annual incidence rate was significantly greater (P less than .001) among males than among females: 20.2 per 100,000 population and 4.1 per 100,000, respectively. The overall mean annual rate was 12.2. A significant increase in the incidence rate in recent years was caused primarily by an increase in the number of sports-related injuries. Secondary hemorrhage occurred in 18 patients (7.3%) and was significantly (P less than .05) more frequent among patients whose initial hyphema filled more than one third of the anterior chamber. The low risk of secondary hemorrhage and associated serious sequelae suggests that the possible benefits from routine systemic administration of aminocaproic acid may not outweigh the costs and risks in populations similar to that of Olmsted County.

Adolescent↗

Prostaglandin F2 alpha-1-isopropylester lowers intraocular pressure without decreasing aqueous humor flow.

Using fluorophotometry, we performed a randomized, dose-response study of the effects of a prostaglandin derivative on aqueous humor flow. Prostaglandin F2 alpha 1-isopropylester, 0.224 micrograms, 0.448 micrograms, and 1.120 micrograms, in saline with polysorbate 80 was instilled into one eye of 20 subjects in three separate dose studies. Polysorbate 80 in saline was instilled in the fellow eye as a control. The drug had no measurable effect on aqueous humor flow or corneal endothelial permeability. Intraocular pressure measured eight hours after administration of the highest dose, 1.120 micrograms, was 20% lower in the treated eye as compared to the fellow eye (P less than .001).

Adult↗

Terbutaline stimulates aqueous humor flow in humans during sleep.

A randomized, double-masked study of the effect of terbutaline sulfate, a selective beta 2-agonist, on the rate of aqueous humor formation was performed in awake and sleeping normal human subjects. The rate of aqueous formation was measured by fluorophotometry. Both the drug- and placebo-treated eyes showed a statistically significant nocturnal reduction of the flow rate (36% suppression in the terbutaline-treated eyes and 43% suppression in the placebo-treated eyes). Terbutaline had no effect on daytime aqueous flow rates, but stimulated flow by 15% during sleep. The drug had no significant effect on intraocular pressure. This study confirms past observations that beta-agonists exert their maximal effects during sleep, when endogenous adrenergic stimulation is at a minimum.

Adult↗

Variations in human corneal endothelial cell morphology and permeability to fluorescein with age.

Fluorophotometry with topically applied fluorescein and endothelial cell photography were performed on 80 normal subjects (age 5-79 yr). Variations in endothelial cell morphology and function, flow of aqueous humor, and intraocular pressure were recorded. The mean endothelial cell size was 332.3 +/- 46.3 micron 2. A 28% increase in endothelial cell size was measured over the eight decades (r = 0.53, P less than 0.001). The coefficient of variation of cell size also increased with age (r = 0.41, P less than 0.001). The percentage of hexagonal endothelial cells decreased by 14% (r = -0.48, P less than 0.001), while the percentage of pentagonal and heptagonal cells increased by 50% (r = 0.44, P less than 0.001) and 40% (r = 0.33, P less than 0.002), respectively, with age. The mean endothelial permeability to fluorescein was 4.03 +/- 0.63 x 10(-4) cm min-1. A 23% increase in endothelial permeability with age was observed (r = 0.44, P less than 0.001). No change in central corneal thickness or endothelial pump rate was found. Flow of aqueous humor remained stable with age, despite a 25% increase in intraocular pressure (r = 0.50, P less than 0.001). Polarization of fluorescence of fluorescein in the corneal stroma decreased with age (r = -0.46, P less than 0.001). We conclude that with age the human corneal endothelium becomes morphologically less regular and may become more permeable to fluorescein.

Adolescent↗

The effects of withdrawal of timolol in chronically treated glaucoma patients.

The dynamics of aqueous humor were studied before and after discontinuing timolol maleate in chronic users. Nineteen patients (mean length of treatment, 44 months) were studied by measuring their baseline intraocular pressure (IOP) and aqueous humor flow during treatment and 2 days to 6 weeks after discontinuing the drug. Flow did not increase significantly until 4 days after discontinuing timolol, and IOP did not increase significantly until 14 days later. Flow did not revert to its normal rate for 2 to 6 weeks. Intraocular pressure was 15% lower and the flow 24% lower during maintenance treatment than 1 month after discontinuing timolol. This comparison demonstrates the efficacy of chronic treatment. Recovery of aqueous flow is slow after stopping timolol. This finding suggests that lower or less frequent doses than are customarily used might be equally efficacious. If timolol is discontinued before filtration surgery, its effects will remain for 2 to 4 weeks.

Adult↗

Aqueous flow is reduced by the alpha-adrenergic agonist, apraclonidine hydrochloride (ALO 2145).

Apraclonidine hydrochloride (ALO 2145), a clonidine derivative that does not cross the blood-brain barrier, was applied topically to one eye of each of 20 normal human subjects. The rate of aqueous humor flow and the permeability of the blood-aqueous barrier were measured by fluorophotometry. Four hours after administration, the flow rate in the apraclonidine-treated eyes was 35% lower than that measured in the control eyes. Three hours after instillation, the intraocular pressure (IOP) was 34% lower in the apraclonidine-treated eyes when compared with control eyes. Both these differences were statistically significant. The drug had little, if any, effect on blood-aqueous permeability.

Administration, Topical↗

A scanning ocular spectrofluorophotometer.

We describe an instrument called a scanning ocular spectrofluorophotometer (SOSF) that measures fluorescence in a two-dimensional cross-section through the anterior chamber and cornea and provides the ability to change excitation and emission wavelengths rapidly. The output of a xenon arc lamp is filtered by a diffraction grating monochromator which has a bandpass of 4 nm and a range of 400 to 800 nm. Light emitted from the fluorophore is filtered by a variable wavelength interference filter which has a bandpass of approximately 11 nm and a range of 400 to 700 nm. To demonstrate the versatility of the instrument, we measured the spectra of fluorescein, fluorescein glucuronide and rhodamine B in the anterior chambers and corneas of pigmented rabbits after topical administration. We also measured simultaneously and independently the redistribution and disappearance of a mixture of fluorescein-labeled dextran and rhodamine B after intracameral injection. Rhodamine B was very rapidly absorbed by the cornea and lens while fluorescein-dextran was not measurable in the cornea before 4 hr. The SOSF provides a means of carrying out spectrofluorophotometry in the living eye and carrying out kinetic experiments which would otherwise be awkward or impossible.

Animals↗

Isoproterenol stimulates aqueous flow in humans with Horner's syndrome.

Topical 1 percent isoproterenol in the presence of the phosphodiesterase inhibitor theophylline was tested for its ability to stimulate the rate of aqueous humor flow through the anterior chamber of the normal and the partially adrenergically denervated human eye (Horner's syndrome). Both the affected eye and the unaffected eye were observed to have lower flows at night than during the day. Isoproterenol had no significant effect on flow during the day in normal eyes or in Horner's syndrome, but during sleep this beta-adrenergic agonist increased flow in the normal eye by 34% and in the Horner's eye by 50%. We interpret the results as indicating that beta-adrenergic activity in the human eye can stimulate aqueous formation under some conditions. However, the observed stimulation could have been due to something other than increased beta-adrenergic activity in the ciliary epithelium.

Adrenergic beta-Agonists↗

6-amino-2-benzothiazole-sulfonamide. The effect of a topical carbonic anhydrase inhibitor on aqueous humor formation in the normal human eye.

The carbonic anhydrase inhibitor, 6-amino-2-benzothiazolesulfonamide, formulated as a 3% suspension in a gel vehicle was instilled in one eye of 21 human subjects in a single dose study to determine its effect on aqueous dynamics. A small but statistically significant effect on aqueous humor flow was observed 2 to 7 hours after application. By 8 hours, the effect had disappeared, and intraocular pressure (IOP) measured 8 hours after application of a single dose was unchanged in these normal volunteers. The drug and its vehicle caused local side effects including irritation, hyperemia, and blurred vision. The authors wondered if multiple doses would produce a greater effect. Four subjects received up to four doses of the drug over 2 days and were restudied. Marked bulbar injection and follicular conjunctivitis, attributable to either the drug or the vehicle, developed in two of the subjects, both contact lens wearers. A milder form of bulbar injection and follicular conjunctivitis developed in a third subject, who received three doses of the drug and was not a contact lens wearer. These side effects precluded additional multiple-dose testing of this formulation of the drug, and no conclusions about the effect of the drug on aqueous flow can be drawn from this portion of the study.

Adult↗

Effect of dexamethasone on corneal endothelial function in Fuchs' dystrophy.

Thirteen patients with Fuchs' endothelial dystrophy were studied to measure the potential effects of topically applied dexamethasone on endothelial function. Endothelial permeability in the Fuchs' dystrophy patients was not different from that found in normal controls. One eye, chosen at random, was treated topically four times a day for 7 days with 0.1% dexamethasone phosphate. The contralateral eye was treated with a placebo of identical appearance. Prior to treatment, there were no statistically significant differences in the means of the intraocular pressure, corneal thickness, endothelial permeability, or endothelial pump rate between the dexamethasone- and placebo-treated groups. In the placebo-treated eyes, a significant decrease was observed in both endothelial permeability and endothelial pump rate over the course of the study. No statistically significant changes occurred in the dexamethasone-treated eyes over the same period. When the dexamethasone group was compared with the placebo group, there was a significant difference in the change in endothelial pump rate between the two groups, attributable in large part to the decrease in pump rate observed in the placebo group over the course of treatment. We interpret our data as lacking support for the concept that topical steroids are beneficial for the treatment of stromal edema in patients with Fuchs' dystrophy.

Adult↗

A method of determining concentration of albumin in the living eye.

A noninvasive method of measuring the concentration of plasma protein in the anterior chamber is described. Fluorescein is applied to the cornea. After the aqueous humor becomes fluorescent, the polarization of fluorescence is measured. The concentration of plasma protein, mainly albumin, can be calculated from the polarization.

Adolescent↗

Effect of long-term contact lens wear on corneal endothelial cell morphology and function.

Anterior segment fluorophotometry (topical) and central endothelial cell photography were performed on 40 long-term (2-23 years) contact lens wearers (four groups of ten each: hard, soft, gas permeable, and gas permeable plus prior lens usage) and 40 non-contact lens wearers of similar ages. Morphologically, the endothelial cells of contact lens wearers showed greater variability in size and shape compared to controls. The mean endothelial cell size in contact lens wearers (307 +/- 35 micron2) was smaller than that of controls (329 +/- 38 micron2, P less than 0.01). There was an increase in the coefficient of variation of cell size of the contact lens group (0.35 +/- 0.06 versus 0.25 +/- 0.04 for controls, P less than 0.0001). The endothelial cell mosaic contained a smaller percentage of hexagonal cells in contact lens wearers (66 +/- 8) compared to controls (71 +/- 7, P less than 0.01). There was a compensatory increase in five-sided cells. Functionally, there was no difference in corneal clarity, central corneal thickness or endothelial permeability to fluorescein (3.78 +/- 0.57 X 10(-4) cm/min versus 3.85 +/- 0.55 X 10(-4) cm/min for controls) between the two groups. Aqueous humor flow was increased 7% in contact lens wearers. We found no correlation between oxygen transmissibility, estimated underlying oxygen tension, or duration of wear of the contact lenses and any morphologic or functional variable. We also found no differences between the four groups of contact lens wearers except that the gas permeable lens wearers had more hexagonal and less pentagonal cells. Long-term contact lens wear induces morphologic changes in the corneal endothelium.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Topical forskolin (colforsin) and aqueous flow in humans.

A 1% forskolin (nonproprietary name, colforsin) suspension was instilled in one eye each of 15 normal human subjects in a single-dose experiment under the following three conditions: during the day, during the night while asleep, and following pretreatment with timolol maleate. The rate of flow was 2.6 +/- 0.13 microL/min (mean +/- SE) in the afternoon in both the treated and the untreated eyes. During sleep at night the flow was lower than in the afternoon in both the placebo-treated eye, 1.5 +/- 0.09 microL/min, and the forskolin-treated eye, 1.3 +/- 0.09 microL/min. Timolol pretreatment reduced the flow to 1.6 +/- 0.08 microL/min in the placebo-treated eye and 1.6 +/- 0.10 microL/min in the forskolin-treated eye. No statistically significant effects of forskolin on flow were observed under any of the conditions. Forskolin caused transient hyperemia in all subjects. The experiment confirmed previous reports of differences in the rate of aqueous flow at different times of day and the effect of the beta-adrenergic blocker timolol on the rate of aqueous humor flow.

Administration, Topical↗

Neodymium: YAG laser damage threshold. A comparison of injection-molded and lathe-cut polymethylmethacrylate intraocular lenses.

The possibility that injection-molded intraocular lenses (IOLs) with imperfections called iridescent clefts could have a decreased threshold to neodymium: YAG (Nd:YAG) laser-induced damage was investigated. Thresholds for Nd:YAG laser-induced damage were determined for injection-molded and lathe-cut polymethylmethacrylate lenses. When aimed at a membrane in contact with a posterior convex surface, the average thresholds were 0.96 +/- 0.18 mJ (Standard deviation [SD]) and 1.80 +/- 0.55 mJ, respectively. The difference was significant at P = 0.001. When injection-molding polymethylmethacrylate was used to make lathe-cut IOLs, very few iridescent clefts were present, and the threshold to Nd:YAG laser-induced damage was 0.94 +/- 0.25 mJ. Iridescent clefts are therefore produced during the injection-molding process but they do not lower the threshold to Nd:YAG laser-induced damage. Rather, the reduced threshold in injection-molded lenses is most probably a result of the polymethylmethacrylate used in their manufacture. Clinically, iridescent clefts in a lens suggest that it has been manufactured by an injection-molding process and that Nd:YAG laser posterior capsulotomy must be performed at the lowest possible energy level to avoid damage.

Lasers↗

Effect of body position on intraocular pressure and aqueous flow.

The relationship between intraocular pressure and the rate of aqueous humor formation was studied in human subjects. Intraocular pressure was altered by changing the subject's gravity-dependent body position. Aqueous humor flow was measured fluorophotometrically. An average change of intraocular pressure of 2.4 +/- 1.2 mmHg and 11.2 +/- 2.7 mmHg was recorded in subjects whose body position was alternated +/- 15 degrees from horizontal and +/- 50 degrees from horizontal. No change of the rate of fluorescein clearance was observed for the milder change of position. A small change of fluorescein clearance was noted in response to the steeper change of position. Changing intraocular pressure seems not to induce compensatory changes in aqueous flow. Therefore we conclude that aqueous formation is relatively pressure-insensitive, a conclusion one would draw from clinical instances of angle-closure glaucoma or as in other systems of secretion, such as the toad bladder or the cerebrospinal fluid, where alterations in pressure do not necessarily influence flow. If there is a regulator of aqueous flow it is not responsive to the changes in intraocular pressure brought about in this study. If aqueous flow regulates intraocular pressure or compensates for changes in intraocular pressure, the signal is not small changes in pressure.

Adolescent↗

Ascorbic acid levels in the aqueous humor of nocturnal and diurnal mammals.

Ascorbic acid concentration is known to be very high in the aqueous humor of humans and most animals. The role it might play in ocular function is a subject of conjecture. Some have proposed that it might protect the eye against light-induced damage. We examined the aqueous humor from 22 species of mammals to determine the range of levels and to see if there was a correlation with behavior. A wide range of ascorbic acid levels in the aqueous humor was found. Most of the animals considered to be diurnal had higher ascorbic acid levels than the nocturnal animals. This would suggest that ascorbic acid in the aqueous humor may play a protective role in those animals who are most exposed to light. Regardless, any theory proposing a role for ascorbic acid in the eye in mammals must take the wide range of ascorbic acid levels into account.

Animals↗

Glaucoma: an overview.

Glaucoma is a potentially blinding ocular disease that commonly affects elderly persons. In this review, we discuss the range of clinical findings, appropriate diagnostic tests, and available medical, laser, and surgical treatment options. New developments in the evaluation of the optic nerve and in visual field testing may facilitate the early detection of glaucoma, and new therapeutic agents hold promise for the future.

Aged↗