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Biomedical subjects

William E Sponsel

Publications and source records attributed to William E Sponsel.

12 recordsLinked to original sources

Dronabinol and retinal hemodynamics in humans.

PURPOSE: To investigate the effects of oral cannabinoids on retinal hemodynamics assessed by video fluorescein angiography in healthy subjects. DESIGN: Interventional study. METHODS: In a self-experiment, the cannabinoid dronabinol (delta-9-tetrahydrocannabinol [THC]) was administered orally to eight healthy medical doctors (7.5 mg Marinol; Unimed Pharmaceuticals, Chicago, Illinois, USA). At baseline and two hours after dronabinol intake, intraocular pressure (IOP) was measured and retinal hemodynamics were assessed by fluorescein angiography. The retinal arteriovenous passage time was determined on the basis of dye dilution curves by means of digital image analysis in a masked fashion. RESULTS: Dronabinol resulted in a significant IOP reduction from 13.2 +/- 1.9 mm Hg to 11.8 +/- 2.0 mm Hg (P = .038). The retinal arteriovenous passage time decreased from 1.77 +/- 0.35 seconds to 1.57 +/- 0.31 seconds (P = .028). Systemic blood pressure and heart rate were not statistically significantly altered. CONCLUSIONS: Cannabinoids, already known for their ability to reduce IOP, may result in increased retinal hemodynamics. This may be beneficial in ocular circulatory disorders, including glaucoma.

Administration, Oral↗

Retinal function assessed by ERG before and after induction of ocular aspergillosis and treatment by the anti-fungal, micafungin, in rabbits.

This study was conducted to evaluate the effectiveness of a new antifungal drug, micafungin, and standard antifungal drugs against endophthalmitis induced in a rabbit by intravitreal injection of Aspergillus fumigatus, an important fungal pathogen. Effectiveness was evaluated by the preservation of b-wave amplitude at 72 h after injection of the fungus relative to the b-wave amplitude at baseline before any intravitreal injections. A 0.06 ml inoculum of 10(6) conidia of A. fumigatus was injected into the vitreous of the right eye of all rabbits; and, 12 h later, a 0.06 ml solution containing one of 3 antifungal drugs or saline was injected into the vitreous of both eyes. All three antifungal drugs produced significant b-wave preservation at 72 h in infected eyes compared to that in infected eyes receiving saline injections. There was no statistically significant difference between the effects of micafungin and amphotericin B in the right eyes with fungal endophthalmitis, and both produced significantly more preservation of b-wave amplitude than voriconazole. Amphotericin B, but neither micafungin nor voriconazole produced significant reduction of the b-wave amplitude in the left eyes.

Amphotericin B↗

Pathogenetic aspects of the glaucomatous optic neuropathy: fluorescein angiographic findings in patients with primary open angle glaucoma.

PURPOSE: To identify and quantify the role of retinal circulation, capillary leakage and/or nonperfusion of the optic nerve head in digital fluorescein angiography in normal subjects and patients with open angle glaucoma. METHODS: Eighteen patients with primary open angle glaucoma (POAG) and 18 healthy age matched subjects were included. Fluorescein angiograms were performed using the scanning laser ophthalmoscope. The arteriovenous passage time (AVP) was assessed by dye dilution technique and describes the shortest passage through a retinal vascular segment. Optic nerve head nonperfusion was marked manually in early angiographic images and is given as percentage of the optic disk area. The fluorescence of the optic nerve head (as measure of the disruption of the blood-brain barrier) and the surrounding retina (ratio of leakage) was measured using digital imaging analysis in the late phases of the angiogram (9-10min). RESULTS: The AVP time was significantly prolonged ( P=0.001) in patients with open angle glaucoma (AVP 2.29+/-0.32 s) compared to healthy subjects (AVP 1.37+/-0.42 s). The mean percentage of the optic nerve head nonperfusion was 16%. The ratio of optic nerve head fluorescence compared to retinal reference loci was significantly increased (P = 0.02) in patients with glaucoma (1.32+/-0.25) compared with normal subjects (1.32+/-0.19). CONCLUSIONS: Fluorescein angiography revealed altered retinal perfusion along with optic nerve head nonperfusion and increased vascular leakage in open angle glaucoma patients. These factors appear to influence each other, with ultrastructural changes of the lamina cribrosa accompanying changes in the vasculature and nerve fibers. Longitudinal and interventive studies should help better elucidate the relationship between circulatory and neural loss, adding vasoprotective therapeutic approaches to interfere with the glaucomatous neurodegenerative chain of events.

Adult↗

Sustained perimacular vascular and visual response to topical beta blockers in normal human eyes.

PURPOSE: To assess visual and circulatory responses to treatment with topical beta adrenergic antagonists. DESIGN: Institutional prospective randomized clinical trial in normal adults. METHODS: Twenty adults (36 (mean) +/- 8 (S.D.) years) underwent repeated baseline perimetry (Humphrey 30-2), contrast sensitivity (Vector Vision), perimacular microcirculatory studies (Oculix blue-field entoptic simulator), intraocular pressure (IOP), heart rate (HR), and blood pressure (BP) testing. Subjects commenced either timolol 0.5% or betaxolol 0.5% twice daily on day 1, were retested on days 3 and 35, discontinued treatment for 21 days, whereupon repeated tests were performed. Treatment responses were compared by paired t-test. RESULTS: Timolol-treated eyes showed improvement in contrast sensitivity (P=0.03) and pericentral perimetric thresholds (P=0.01), but corresponding increases among betaxolol-treated eyes were significantly higher (P=0.03 and 0.04, respectively, relative to timolol-treated eyes). Leukocyte velocity increased with both drugs, each with post-withdrawal carryover (P< or =0.03). Significant IOP reduction (approximately 2.5 mmHg) occurred in both groups, BP fell 2.8 mmHg among betaxolol-treated subjects (P=0.02), and HR was 2 bpm slower among timolol-treated subjects (P=0.03), but all reverted to baseline values after washout. CONCLUSIONS: Both treatment groups demonstrated significant changes in visual function and perimacular hemodynamics, sustained after the terminal 3-week washout period.

Administration, Topical↗

Operative revision of non-functioning filtering blebs with 5-fluorouracil to regain intraocular pressure control.

PURPOSE: To determine the efficacy of extensive microsurgical needling revision of failed filtering blebs followed by serial 5-fluorouracil subconjunctival injections. METHODS: Thirty-six eyes of 34 consecutive patients with progressive open-angle glaucoma refractory to topical therapy submitted to needling revision as a major procedure. All patients required multiple antiglaucoma medications preoperatively, and had completely flat or densely encapsulated filtering blebs. All patients underwent elaborate needling revision (limbus to superior rectus >8 mm diameter, >3 mm elevation, entry-site sutured with 8-0 vicryl and bleb reformed via paracentesis with viscoelastic) in the operating room, followed by serial 5-fluorouracil. The patients were followed for up to 6 months postoperatively. The main outcome measures were intraocular pressure (IOP) and the number of antiglaucoma medications used. RESULTS: Thirty-one eyes (86%) maintained mean IOP below 15 mmHg postneedling without medication. Overall the mean IOP postneedling was >9 mmHg lower than medicated preoperative levels (P < 0.0001). IOP reduction in encapsulated blebs was marginally superior to that in flat blebs. CONCLUSIONS: Extensive needling revision in the operating room is safe, straightforward, and produces reproducible restoration of filtering function.

Adult↗

Determination of voriconazole in aqueous humor by liquid chromatography-electrospray ionization-mass spectrometry.

A novel method based on liquid chromatography-mass spectrometry with electrospray ionization (LC-MS) has been developed for analysis of voriconazole in aqueous humor. The separation was achieved on a reversed-phase C(18) column eluted by 70% acetonitrile-30% water-0.01% TFA. The correlation between the concentration of voriconazole to peak area was linear (r(2)=0.9990) between 0.04 and 60 ng, with a coefficient of variance of less than 3%. Limit of quantitation (LOQ) was estimated to be 5 ng/ml voriconazole with an injection volume of 2 microl of aqueous humor. Both intra-day and inter-day imprecision were less than 3% over the whole analytical range. Parallel analyses of voriconazole samples by LC-MS and by high-performance liquid chromatography (HPLC)-UV showed that the two methods were highly correlated (r(2)=0.9985). LC-MS was used to the determine voriconazole levels achieved in the aqueous humor of the rabbit eye, following topical application of 5 or 10 microg voriconazole in the form of eyedrops for 11 days b.i.d. The lower dosage produced an aqueous humor concentration of 7.29+/-5.84 microg/ml, while the higher dosage produced a concentration of 14.56+/-12.90 microg/ml.

Animals↗

Latanoprost and brimonidine: therapeutic and physiologic assessment before and after oral nonsteroidal anti-inflammatory therapy.

PURPOSE: To assess, before and during oral nonsteroidal anti-inflammatory drug coadministration, latanoprost's and brimonidine's hypotensive action in eyes at risk of glaucomatous progression, assessing the effect of each drug on ocular perfusion and visual function. METHODS: Twenty consenting adults with open-angle glaucoma or ocular hypertension underwent a double-masked, bilateral, randomized prospective study. Treatment started with either latanoprost 0.005% in the morning and placebo in the evening, or brimonidine 0.2% twice daily in one eye; after 1 week starting the other in the fellow eye. After another week, oral indomethacin 25 mg four times a day, commenced for 2 more weeks. Intraocular pressure, ocular circulation, and visual function were monitored pretreatment, after unilateral monotherapy (day 7), bilateral ocular therapy (day 14), and coadministered oral indomethacin (day 28). Intrasubject differences (interocular and intraocular relative to baseline) were determined by two-tailed paired t test. RESULTS: A loss of the significance of intraocular pressure reduction with brimonidine was noted after oral indomethacin coadministration (-14%; P =.004 for brimonidine alone versus -11%; P =.3 with indomethacin). Significant intraocular pressure reduction with latanoprost persisted despite indomethacin (-25%; P <.0001 for latanoprost alone versus -30%; P <.0001 with indomethacin). Pulsatile ocular blood flow increased 40% with latanoprost, but was unchanged with brimonidine (interdrug difference, P =.004). Midperipheral retinal microcirculation increased 23% (P =.03) with latanoprost. Humphrey perimetry and contrast sensitivity remained consistently at or above baseline with both latanoprost and brimonidine. Indomethacin had no significant effect on ocular perfusion or visual function measures. CONCLUSIONS: Circulatory and hydrodynamic findings differed substantially for the two drugs. The loss of significance of intraocular pressure reduction with brimonidine during indomethacin treatment may be clinically important.

Administration, Oral↗

Comparative effects of latanoprost (Xalatan) and unoprostone (Rescula) in patients with open-angle glaucoma and suspected glaucoma.

PURPOSE: To compare, in paired eyes of open-angle glaucoma patients and glaucoma suspects, hydrodynamic and visual changes after 1 month of topical latanoprost in one eye and unoprostone in the other. DESIGN: Single-center, institutional randomized clinical trial. METHODS: After completing a washout period off all topical medication, 25 adults (mean age 54 +/- SEM 2 years) with bilateral open-angle glaucoma or glaucoma suspect status underwent morning (8 to 10 AM) and afternoon (1 to 3 PM) measurements of intraocular pressure (IOP), pulsatile ocular blood flow (POBF), contrast, sensitivity, frequency doubling technology, and Humphrey 10-2 perimetry (HVFA II) in both eyes. Each then started unoprostone 0.15% (Rescula) in one randomly assigned eye and latanoprost 0.005% (Xalatan) in the other. Unoprostone was administered at 8 AM and 8 PM and latanoprost at 8 PM with placebo at 8 AM, both from masked bottles. After 28 days, differences were determined for each measured variable by two-tailed paired t test. RESULTS: Starting from similar baseline IOP levels, after 1 month of treatment, the mean morning IOP values differed according to the topical agent received (16.2 +/- SEM 0.6 mm Hg for latanoprost vs 17.9 +/- 0.7 mm Hg for unoprostone; P =.001). These morning pressures were 2.6 mm Hg lower than baseline in the eyes receiving latanoprost (P <.0001), and 1.6 mm Hg lower in unoprostone-treated eyes (P =.02). Afternoon values were 3.1 +/- SEM 0.6 lower than corresponding baseline in eyes receiving latanoprost, and 2.4 +/- SEM 0.6 mm Hg in unoprostone-treated eyes (P <.0001 from baseline for both medications; interdrug mean IOP difference; P =.04). Eyes receiving unoprostone showed a 1.7-db improvement in frequency doubling mean deviation (P =.03), the only significant visual function change observed. Pulsatile ocular blood flow increased 30% relative to baseline in eyes receiving latanoprost, (P <.0001) and 16% in eyes receiving unoprostone (P =.05) by the morning of day 28. That afternoon, mean POBF had increased 30% (P <.0001) relative to afternoon baseline values among eyes receiving latanoprost and 18% (P =.03) among those receiving unoprostone (interdrug change difference, P =.05). Humphrey perimetry and contrast sensitivity remained stable with both prostanoids. CONCLUSIONS: Both latanoprost and unoprostone produced significant reductions in IOP and increases in POBF, with stable central and perimacular visual function. Latanoprost once daily produced IOP reduction and POBF increases nearly twofold greater than those obtained with unoprostone twice daily. These differences in IOP and POBF change between unoprostone and latanoprost were statistically significant.

Adult↗

Comparison of the frequency doubling technology screening algorithm and the Humphrey 24-2 SITA-FAST in a large eye screening.

PURPOSE: To compare the Frequency Doubling Technology (FDT) C20-1 screening algorithm and the Humphrey Field Analyser II (HFA) 24-2 SITA-FAST in a large eye screening. METHODS: In a non-randomized, prospective, free eye screening, the FDT Screening Protocol (C20-1 Screening Algorithm) was administered to 574 attendees (422 men and 152 women, average age 64, range 17-89 years) of the 1998 Veterans of Foreign Wars (VFW) Convention in San Antonio, Texas. Individuals who failed the FDT (two or more misses out of 17 locations) immediately underwent white-on-white threshold visual field perimetry (HFA 24-2, SITA-FAST). Humphrey visual field analysis included STATPAC and masked evaluations by three glaucoma specialists. RESULTS: Approximately one-tenth of the VFW conference attendees voluntarily presented themselves for screening. Among these 574 volunteers, 69 (12%) failed the FDT and underwent HFA analysis. Eighty-one per cent (56/69) of these FDT failures had abnormal HFA Glaucoma Hemifield Tests. Eighty-eight per cent (61/69) were judged to have nerve fibre type visual field loss on HFA by at least two of three masked examiners. A positive correlation existed between the number of FDT locations missed and the HFA mean deviation (r = 0.5, P = 0.0001). A similar association was observed when FDT and HFA results were analysed by quadrant (r = 0.5, P < 0.0001). CONCLUSION: There was a low false positive rate and a good positive predictive value comparing the FDT screening algorithm to the HFA 24-2 SITA-FAST in this study. This supports the potential use of FDT as an economical screening device.

Adolescent↗