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Biomedical subjects

W E Sponsel

Publications and source records attributed to W E Sponsel.

At least 19 recordsLinked to original sources

Modification of the Heidelberg retinal flowmeter to record pattern and flicker induced blood flow changes.

PURPOSE: We tested a prototype stimulator interfaced with a commercially available scanning laser ophthalmoscope designed to measure retinal capillary perfusion (Heidelberg Retina Flowmeter (HRF)). The add-on stimulator optically superimposed the image of a monitor display on to the subject's retina coaxially with the imaging optics of the HRF. The purpose of the study was to determine if flicker and pattern stimulation presented in this manner could evoke changes in retinal perfusion that could be measured by the HRF. METHODS: The prototype stimulator projected 55 degrees visual angle circular fields of homogeneous flicker, alternating checkerboard, and multi-focal m-sequence hexagonal patterns on the retina of 10 human subjects during acquisition of images by the HRF. RESULTS: Images were successfully acquired and processed. HRF perfusion values during flicker and pattern stimulation were not significantly different from control values. CONCLUSIONS: Results of the present study and a previously published study showing a flicker-induced increase in the HRF perfusion values are contradictory. Retinal perfusion measured by the HRF were not affected by flicker and pattern stimulation delivered through the prototype device. These data are not consistent with a large flicker or pattern induced increase in retinal perfusion. The instrumental modification appears promising. However, the raster scan stimulation technique or some other aspect of stimulation or image acquisition may account for the different results in the present study and previous studies in our laboratory and in the laboratories of other investigators.

Adult↗

Genetic mapping of a novel X-linked recessive colobomatous microphthalmia.

Colobomatous microphthalmia is a common ocular malformation with a heterogeneous phenotype. The majority of cases without associated systemic abnormalities have an autosomal dominant inheritance pattern [McKusick, 1990: Mendelian inheritance in man]. A few isolated cases with autosomal recessive transmission have been described [Zlotogora et al., 1994: Am J Med Genet 49:261--262]. To our knowledge, no cases of X-linked colobomatous microphthalmia that are not a part of a syndrome or a multisystem disorder have been reported. In this study, we describe a genetic and clinical evaluation of a large pedigree in which colobomatous microphthalmia is segregating in an X-linked recessive fashion. Based on recombination breakpoint analysis, we have determined that the critical interval exists between markers DXS989 and DXS441, placing the disease locus on the proximal short arm or the proximal long arm of the X chromosome. Using linkage analysis, we obtained two-point lod scores of 2.71 at zero recombination with markers DXS1058, DXS6810, DXS1199, and DXS7132. Overlapping multipoint analysis established a broad maximum from marker DXS1068 to marker DXS7132, a region spanning approximately 28 cM. This study provides evidence for the presence of a new locus for colobomatous microphthalmia.

Adolescent↗

Sildenafil increases ocular perfusion.

PURPOSE: Our goal was to determine whether visual system responses to sildenafil accompany shifts in ocular perfusion. The human choroid, which supports the metabolic function of the outer retina, is an erectile tissue, analogous in many respects to the corpus cavenosum. METHODS: Right eyes of 12 normal adults were evaluated before and 2 h after 50 mg oral dose of sildenafil. Pulsatile ocular blood flow (POBF), intraocular pressure (IOP), Heidelberg retinal flowmetry (HRT), 4.26 cpd, 7.5 Hz temporally-modulated contrast sensitivity (CS), full-threshold C-20 frequency doubling technology (FDT) perimetry, and blood pressure (BP) were measured. RESULTS: POBF (+29.4%; p > 0.016) and CS (+33.6%; p > 0.014%) increased within 110 (+/-7.7) minutes after sildenafil administration. No subject demonstrated decreases in either variable. HRF flow values increase among 7 of the 9 eyes producing stable scans (+8.2%; p > 0.1). FDT values did not change significantly, nor did systemic pulse amplitude or mean IOP. CONCLUSIONS: Since IOP and systemic pulse amplitude both remained stable after sildenafil administration, while POBF values increased to a level nearly one third greater than baseline. It appears sildenafil can induce intrinsic change in the choroidal vasculature, with an apparently positive impact on pericentral contrast sensitivity. This effect may be of clinical utility.

Administration, Oral↗

Frequency of sustained glaucomatous-type visual field loss and associated optic nerve cupping in Beaver Dam, Wisconsin.

PURPOSE: To determine the prevalence of persisting glaucomatous-type visual field loss in a Midwestern American adult population, in association with four grades of disc cupping. METHODS: On two separate occasions (1988-1990 and 1993-1995) 2955 predominantly Caucasian adults aged 43-84 provided medical history, underwent applanation tonometry, slit-lamp examination, quantitative suprathreshold perimetry and stereoscopic disc analysis as part of the National Institutes of Health-sponsored Beaver Dam Eye Study. Those demonstrating evidence of glaucomatous-type visual field loss at both visits were the subject of the present analysis. Among these individuals, associations were determined for four categories of optic disc cupping (vertical cup/disc < 0.5, > 0.5, > 0.6, > 0.8), intraocular pressure, blood pressure, cardiovascular pathology and prior glaucoma diagnosis. RESULTS: Of the 2955 subjects assessed, 120 (4%; 57 women, 63 men) demonstrated glaucomatous-type visual field defects at each visit. Fifty-five of these 120 (2% of the tested population) also exhibited some degree of disc cupping in a related eye at both visits. Among these 2%, positive associations relating the extent of field loss, cupping and intraocular pressure were confirmed, but the majority in each cupping category had normal eye pressures. Only seven of the 120 were aware of the presence or suspicion of eye disease prior to the screening. CONCLUSIONS: A majority of those found to have visual field loss and optic nerve cupping persisting together in the same eye after 3-5 years had normal pressures in each eye at both visits. Despite good access to medical care, very few who demonstrated persisting cupping and field loss (even among those with elevated eye pressure) were aware of their ocular condition through prior contact with an eye care professional.

Aged↗

Effects of latanoprost and timolol-XE on hydrodynamics in the normal eye.

PURPOSE: To compare the effects of latanoprost and timolol-XE on ocular pressure and perfusion in healthy adults, with respect to episcleral venous pressure. METHODS: A double-masked, placebo-controlled crossover study of weeklong bedtime treatment with one drop of drug, with placebo contralaterally, followed by a 3-week washout and alternate-drug/contralateral-placebo repeat. Intraocular pressure was measured by applanation and by pneumotonometry, providing pulsatile ocular circulatory estimates. Measurements of episcleral venous pressure were obtained (Friberg method). RESULTS: Twenty subjects participated (five men, 15 women; mean age, 39 years (range, 21 to 55 years); mean baseline intraocular pressure, 13.4 mm Hg). A greater decrease in intraocular pressure was seen among these subjects the morning after initiating treatment with latanoprost (-2.0 mm Hg; P <.0001) than with timolol-XE (-0.9 mm Hg; P =.051) (latanoprost versus timolol DeltaP =.008). This ocular hypotensive effect remained significant that evening with latanoprost (-3.2 mm Hg; P <.0001) but not with timolol XE (-1.0 mm Hg; P =.2). By the morning of day 8, mean intraocular pressure remained 3.2 mm Hg below baseline with latanoprost and 2.3 mm Hg below baseline with timolol-XE (P <.0001 for both drugs). Neither drug altered episcleral venous pressure. Among a subgroup of nine subjects with comparable intraocular pressure reductions with the two drugs, latanoprost treatment was associated with a 16.7% increase in mean pulsatile ocular blood flow (P =.04) through the weeklong treatment interval, consistently higher than during timolol-XE treatment of the same subjects. CONCLUSION: Latanoprost caused an overnight decrease in intraocular pressure in normotensive normal eyes, and both drugs significantly reduced intraocular pressure within 1 week. Intraocular pressure remained higher than episcleral venous pressure throughout treatment with both drugs. Latanoprost was associated with enhanced pulsatile ocular perfusion not seen with timolol-XE treatment.

Adrenergic beta-Antagonists↗

Periocular accumulation of timolol and betaxolol in glaucoma patients under long-term therapy.

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.

Adrenergic beta-Antagonists↗

Clinical classification of glaucomatous visual field loss by frequency doubling perimetry.

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.

Algorithms↗

Dorzolamide hydrochloride and visual function in normal eyes.

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.

Adult↗

Association of retinal capillary perfusion with visual status during chronic glaucoma therapy.

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.

Administration, Topical↗

Retinal capillary hemodynamics and VEP/pressure tolerance: evidence of retinal microcirculatory compromise in treated glaucomatous eyes.

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.

Adrenergic beta-Antagonists↗

A comparison of postoperative complications from pressure-ridge Molteno implants versus Molteno implants with suture ligation.

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.

Female↗

Acute IOP elevation with scleral suction: effects on retrobulbar haemodynamics.

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.

Acute Disease↗

Macular capillary particle velocities: a blue field and scanning laser comparison.

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.

Adult↗