Sildenafil and ocular perfusion.
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Biomedical subjects
Publications and source records attributed to W E Sponsel.
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PURPOSE: To determine if betaxolol or timolol is present in measurable concentration in the Tenon capsule in patients under long-term topical therapy. METHODS: Small (1-cc) specimens of Tenon capsule were removed at the time of filtering surgery from 15 glaucoma patients under long-term preoperative topical therapy, nine of whom had been treated with timolol and six of whom had been receiving betaxolol. Methanol extracts of these tissue samples were analyzed quantitatively for the presence of either beta-adrenergic antagonist by high-performance liquid chromatography. RESULTS: Drug was detected in every specimen. A mean total of 2.6 (range, 0.1-30.0) microg of betaxolol was detected per 1-cc specimen. CONCLUSION: Timolol and betaxolol penetrate the conjunctiva and accumulate in the Tenon capsule. In patients under long-term therapy, the periocular tissue can accumulate a greater quantity of beta-antagonist than is present in a daily dosage of applied eyedrops, manyfold higher than the maximal intraocular concentration.
PURPOSE: To determine whether the frequency doubling perimeter (FDP) can grade glaucomatous visual function loss in a clinically relevant manner. Sinusoidal gratings < 1 cpd that undergo counterphase flicker > 15 Hz appear to have twice as many bands of light, a phenomenon referred to as the "frequency doubling illusion." Evidence suggests that this psychophysical effect is mediated in part by large-diameter ganglion cells, which are reported to be lost early in the glaucomatous disease process. A portable, commercially available FDP has already demonstrated high diagnostic potential for glaucoma screening. METHODS: Sixty-four eyes of 42 glaucomatous patients and 22 eyes of 14 normal subjects were evaluated by means of both frequency doubling perimetry and Humphrey perimetry. A clinical scoring algorithm modeled after the Hodapp-Parrish-Anderson criteria for scoring Humphrey visual field defects was derived for the FDP at the halfway point of the study, and all participants were reassessed with this algorithm upon its completion. RESULTS: FDP mean and pattern deviation showed strong linear correlations with Humphrey 30-2 mean deviation (R = 0.75; P < .0001) and corrected pattern standard deviation values (R = 0.64; P < .0001). Despite this, neither global index could consistently categorize the graded glaucomatous visual fields in a manner consistent with the Hodapp-Parrish-Anderson criteria. The new FDP scoring algorithm did provide good segregation (73% precise parity, 93% parity within one Humphrey grade). CONCLUSIONS: Sixteen-zone frequency doubling perimetry can segregate glaucomatous visual field loss into pathologic categories approximating those obtained with Humphrey 30-2 perimetry by means of a formula modeled after the Hodapp-Parrish-Anderson criteria.
PURPOSE: To determine by a pilot study whether standard treatment with the topical carbonic anhydrase inhibitor dorzolamide hydrochloride influences visual function under normal breathing conditions, during carbon dioxide inhalation, or during hyperventilation, and to establish criteria for future larger-scale studies. METHODS: We enrolled 12 normal subjects into this randomized double-masked placebo-controlled crossover study. Each subject was treated with either dorzolamide 2% or placebo, three times daily, for 4 days. After a 2-week washout period, the alternative topical agent was used under identical testing conditions. On day 2 of each treatment phase, contrast sensitivities to sinusoidal gratings of 1 and 4 cycles per degree (cpd) were assessed. On day 4, mean deviation values from full-threshold 10-2 visual fields were obtained. Three sets of each visual function test were obtained before each treatment phase, and in sequence on each testing day, during normal breathing (baseline), inhalation of carbon dioxide-enriched air, and hyperventilation while intraocular pressure was monitored. RESULTS: Contrast sensitivity at 4 cpd decreased significantly (P < .01) during carbon dioxide supplementation with placebo but showed no significant change with dorzolamide. The decrease in contrast sensitivity accompanying hyperventilation was attenuated (by nearly 50% at 1 cpd) during dorzolamide treatment. Dorzolamide treatment was associated with higher perimetry mean deviation values under each treatment condition and was statistically significant (P < .05) at baseline. CONCLUSIONS: Dorzolamide appears to enhance contrast sensitivity in normal subjects during physiologic hypercapnia and hypocapnia at 4 and 1 cpd, respectively. Also, under normal breathing conditions, dorzolamide therapy increases perimetric light sensitivity.
PURPOSE: The purpose of the study is to determine whether retinal microcirculation is associated with the degree of visual function in glaucomatous eyes receiving chronic bilateral medical therapy with topical beta-blockers. METHODS: A nonrandomized, 3-year prospective clinical study was undertaken on 37 patients with glaucoma and normal visual acuity receiving symmetric topical medication in both eyes. Humphrey 30-2, Henson CFA 2000, and Vistech 3 and 6 cycles/degree contrast sensitivity were obtained bilaterally at multiple visits, along with Oculix 1000 blue-field estimates of perimacular leukocyte velocity. The mean asymmetry of measurements obtained throughout the treatment period for each pair of eyes was determined, and correlations were obtained to assess visual function asymmetry circulatory asymmetry. RESULTS: Significant associations were observed between blue-field entoptic capillary leukocyte velocity measurements and those for all three visual function testing methods, the eye with the superior vision typically having the higher mean leukocyte velocity (P < 0.001 for both Humphrey mean deviation and Henson perimetry, P < 0.002 for Humphrey corrected pattern standard deviation, and P < 0.02 for contrast sensitivity at both 3 and 6 cycles/degree). CONCLUSIONS: Central retinal microcirculation is associated with various measures of central and peripheral visual function in glaucomatous eyes receiving beta-adrenergic blocker therapy.
Measurements of retinal leukocyte velocity were made in single eyes of 6 glaucomatous adults and 9 normal subjects at each of 4 discrete levels of IOP elevation assigned according to the characteristics of prior pattern-evoked cortical potential pressure tolerance measurements. Glaucomatous eyes failed to demonstrate any stabilization in retinal leukocyte velocity at pressures above 45 mm Hg, with velocities 33% lower than normal for a comparable degree of IOP elevation (p < 0.012). Even at baseline IOP, leukocyte velocity was 27.2% slower in the treated glaucomatous eyes than in normal control eyes (p < or = 0.013), despite comparable baseline IOP levels in both groups.
BACKGROUND AND OBJECTIVES: The pressure-ridge Molteno implant incorporates a ridge on the proximal episcleral plate to limit aqueous outflow during the immediate postoperative period. This modification is intended to decrease the high incidence of postoperative hypotony and flat anterior chambers following Molteno tube implantation, while avoiding the pressure spikes that can occur with suture ligation of the Molteno tube. This study was devised to compare postoperative intraocular pressure control and complications associated with pressure-ridge Molteno implantation versus a standard Molteno implantation with suture ligation of the tube. PATIENTS AND METHODS: Thirty eyes were prospectively randomized to receive either a pressure-ridge, double-plate Molteno implant or a standard, double-plate Molteno Molteno implant with suture ligation of the tube. RESULTS: Postoperative intraocular pressure was significantly higher at day 1 and week 2 in the suture-ligation implant group, although the final pressure at 12 weeks was not different between the two groups. Six of 15 eyes from the pressure-ridge implant group experienced shallow or flat anterior chambers with hypotony, whereas 5 of 15 eyes from the suture-ligation implant group had significant postoperative pressure spikes. CONCLUSION: Because the ridge effect is unpredictable, further modifications are necessary to prevent postoperative hypotony.
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AIMS/BACKGROUND: Mechanical and vascular factors may both contribute to glaucoma. This study investigated the relation of mechanical to vascular factors by examining how acute IOP elevation altered flow velocities in the central retinal and ophthalmic arteries. METHODS: IOP was elevated from a baseline near 14 to approximately 45 mm Hg using suction ophthalmodynamometry. During recovery from scleral suction, IOP fell to near 8 mm Hg. At each IOP, peak systolic and end diastolic velocities (PSV and EDV) were measured in the central retinal and ophthalmic arteries using colour Doppler imaging (Siemens Quantum 2000). Eleven healthy people served as subjects. RESULTS: Acute elevation in IOP had no effect upon PSV, EDV, or the derived resistance index in the ophthalmic artery: flow velocities in this vessel were identical at IOP of 8 mm Hg or 45 mm Hg. In contrast, in the central retinal artery, PSV and EDV fell, and the resistance index rose, in steady progression as IOP was acutely elevated (each p < 0.01). At IOP of 45 mm Hg, EDV was virtually absent and the resistance index was very nearly 1.0. CONCLUSION: Ophthalmic arterial haemodynamics are unrelated to acute fluctuations of the IOP over a wide range, suggesting that ocular hypertension itself cannot induce vascular dysfunction in this artery. In contrast, flow velocities in the central retinal artery were highly IOP dependent, implying that haemodynamic and mechanical factors are closely linked in this vascular bed.
BACKGROUND: Two different techniques are available for measurement of macular capillary particle velocities. The psychophysical blue field simulation technique gives data on macular leukocyte flow velocities, while the scanning laser technique provides information on capillary blood velocities of hypofluorescent segments in the macular network. Published velocity data differ considerably between the two methods. The current study was undertaken to compare the two measuring techniques in a group of healthy volunteers. METHODS: Thirty-two healthy subjects (12 man, 20 women, mean age 27 years) participated in this study. All subjects underwent entoptic leukocyte visualization by means of blue field simulation followed by fluorescein angiography using scanning laser ophthalmoscopy. RESULTS: The capillary blood velocities measured using the scanning laser technique were significantly higher (P < 0.01) than the flow velocities estimated with the blue field simulation technique (2.68 +/- 0.3 mm/s vs 0.89 +/- 0.2 mm/s). No significant correlation between the flow velocities was found (r = -0.22). CONCLUSION: The differences may be related to different measuring locations and/or measurements of different phenomena. The blue field technique estimates average leukocyte flow in the macular network, whereas the scanning laser technique quantifies the velocity of erythrocyte aggregates in the capillary lumen of the para- and perifoveal network. A combination of both techniques may be helpful in interpreting physiological responsiveness and altered velocity pattern in diseased eyes.
PURPOSE: To assess the screening efficacy and practical use of two portable devices to detect moderate to severe visual field loss rapidly in population screening. METHODS: Henson visual field analysis and Damato campimetry for glaucoma were performed in a healthy adult population, to determine false-positive rates; in established glaucoma patients and suspects, to determine false-negative rates; and in a general adult population, to assess practical use in actual screenings. RESULTS: There were no false-positive test failures among the 82 normal subjects who completed the Henson two-step screening. Eighty of 83 normal subjects passed Damato campimetry, resulting in a false-positive rate of 3.6%. Among 83 glaucoma suspects and patients, the Henson test identified 49 (84%) of 58 subjects whose full-threshold fields from Humphrey perimetry were abnormal, 38 (97%) of 39 of whom had moderate to severe visual field loss. The Damato campimeter detected 55 (81%) of 68 subjects with any pathologic loss on full-threshold visual fields, 44 (92%) of 48 of whom had moderate to severe visual field loss. Among 1,278 subjects tested in general population screenings, 55 subjects (4.3%) failed either or both tests. CONCLUSIONS: The Henson visual field analyzer can discriminate moderately to severely diseased from normal visual fields with high sensitivity and specificity. The Damato campimeter can reliably detect moderate to severe visual field loss with a tolerably low false-positive rate. To overcome the weakness of glaucoma screening by tonometry alone, some forms of visual field testing may be acceptably brief (cost effective) and accurate (sensitive and specific).
Fluorescein angiograms were performed to evaluate perifoveal capillary blood velocities (v), capillary density (perifoveal intercapillary areas: PIA) and the foveal avascular zone (FAZ) by means of the scanning laser technique (SLO-101 Rodenstock). The angiograms were digitally stored and the data quantified off-line with an image analyzing system (IBAS). In the present study 46 patients with non-insulin-dependent diabetes mellitus (NIDDM) were examined and their data compared with that of 31 healthy volunteers. The perifoveal capillary flow velocity of the NIDDM subjects (v = 2.33 +/- 0.36 mm/s) was significantly (P < 0.01) decreased as compared to healthy subjects (v = 2.86 +/- 0.41 mm/s). The perifoveal intercapillary areas in the foveal avascular zone were significantly increased in patients with NIDDM (PIA = 10029 +/- 3402 microns2; FAZ = 0.415 +/- 0.272 mm2) as compared with healthy subjects (PIA = 3965 +/- 467 microns2; FAZ = 0.221 +/- 0.071 mm2). These data suggest the possibility that a decrease in perifoveal capillary blood velocities in combination with decreased capillary density (enlarged PIA) and an enlargement of the foveal avascular zone may occur in patients with NIDDM. The determination of these parameters could help in monitoring the progress of diabetic retinopathy and diabetic maculopathy.
A recent study found that the gold foil electrode produces large pattern electroretinogram amplitudes, but the test-retest reliability was low. In a three-center study, we observed that 90% of 29 patients who were tested with gold foil electrodes used three times appeared to have markedly lower amplitudes than when tested with new electrodes during the same session. Across study centers, the mean of the new electrode recordings was 3.78 microV (standard deviation, 1.13 microV), versus 2.93 microV (1.29 microV) for used electrodes. This 0.85-microV reduction (22%) was statistically significant (F = 7.10 p = 0.01). Electrodes used three times demonstrated an average change in the coefficient of variation of 14% (standard deviation/mean = coefficient of variation; new, 1.13/3.78 = 30%; used, 1.29/2.93 = 44%). Two of the study sites (Houston/Indianapolis) conducted test-retest pattern electroretinograms on a total of 18 patients and found the mean evoked potential to be 3.55 microV with new electrodes and 2.82 microV with used electrodes. The coefficient of variation for the test-retest data was 30% and 47% for new and used electrodes, respectively. Light microscopy showed small cracks on the surface of the electrode, with the number and configuration of the cracks varying in each electrode. The presence of cracks is further complicated by their proximity to the tear film. These sources of variation can result in significantly different impedances. We propose that constant flexion, as a result of patient blinking, causes cracks in the thin gold surface of the electrode. Used electrodes will produce lower pattern electroretinogram amplitudes and poor test-retest reliability.(ABSTRACT TRUNCATED AT 250 WORDS)
There is a conflicting literature regarding the possible presence of adrenergic innervation of the retinal circulation. The effect of a histologically confirmed left superior cervical ganglionectomy on the total retinal blood flow in eight anaesthetised female cynomolgus monkeys was determined. Near total unilateral ocular sympathetic denervation was confirmed by ipsilateral miosis, supersensitivity of pupillary dilatation to topical phenylephrine and pupillary hyporesponsiveness to topical hydroxyamphetamine. Retinal vein diameters were measured from monochromatic photographs, maximum red cell velocities (Vmax) were measured with a helium-neon laser, using a bidirectional laser Doppler velocimeter technique, and the total retinal blood flow in each eye was determined by summation of measurements of flow in individual retinal veins. Mean (SEM) total retinal blood flow was 32.93 (1.49) and 30.41 (1.86) microliters/min in the eight sympathectomised and normal eyes respectively; the 9% (5%) difference was not statistically significant. Our study suggests that pharmacologically confirmed sympathetic denervation has little if any effect on resting total retinal blood flow.
PURPOSE: Recent studies suggest that elevated intraocular pressure is not the only causative factor for the development of visual field loss and optic nerve damage in glaucomatous eyes. The authors determine whether retinal hemodynamics or blood fluidity are alternated in eyes of patients with open-angle glaucoma compared with those of age- and sex-matched healthy subjects. METHOD: High-quality video fluorescein angiograms were obtained from single eyes of 51 patients with chronic open-angle glaucoma. From these angiograms, the arm-retina time, mean dye velocity, and arteriovenous passage time were quantified. The data from patients were compared with those of an age- and sex-matched group of healthy subjects. RESULTS: In patients with chronic open-angle glaucoma, an 11% reduction of the mean dye velocity (P < 0.05) and a 41% prolongation of the arteriovenous passage time (P < 0.01) was observed relative to the values obtained among the control subjects. Among hematocrit values, plasma viscosity, and erythrocyte aggregation, only plasma viscosity showed a significant increase (4%; P < 0.01) in patients with chronic open-angle glaucoma. CONCLUSION: These results indicate that a pronounced circulatory deficit exists within the retinal vasculature of glaucomatous eyes, which may coexist with, but cannot be fully attributed to, an increase in plasma viscosity.
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PURPOSE: The purpose of this study is to determine the prevalence of glaucoma in the population participating in the Beaver Dam Eye Study (n = 4926). METHODS: All subjects were examined according to standard protocols, which included applanation tonometry, examination of the anterior chamber, perimetry, grading of fundus photographs of the optic disc, and a medical history interview. Visual field, cup-to-disc ratio, and intraocular pressure (IOP) criteria were used to define the presence of open-angle glaucoma. Definite open-angle glaucoma was defined by the presence of any two or all three of the following: abnormal visual field, large or asymmetric cup-to-disc ratio, high IOP. RESULTS: The overall prevalence of definite open-angle glaucoma was 2.1%. The prevalence increased with age from 0.9% in people 43 to 54 years of age to 4.7% in people 75 years of age or older. There was no significant effect of sex after adjusting for age. Of the 104 cases of definite open-angle glaucoma, 33 had IOPs less than 22 mmHg in the involved eye. Hemorrhage on the optic disc was found in 46 people; 2 of these had glaucoma. Narrow-angle glaucoma was rare, with two definite cases in the population. CONCLUSION: The prevalence of open-angle glaucoma in Beaver Dam is similar to that in other white populations. Findings from this study re-emphasize the notion that estimates of glaucoma prevalence should be based on assessing multiple risk indicators.