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Biomedical subjects

T J Zimmerman

Publications and source records attributed to T J Zimmerman.

At least 19 recordsLinked to original sources
PubMed1998

Anterior uveitis associated with latanoprost.

PURPOSE: To report the association of anterior uveitis with the use of latanoprost. METHODS: We studied four patients with complicated open-angle glaucoma who had anterior uveitis associated with the use of latanoprost. The uveitis was unilateral and occurred only in the eye receiving latanoprost in three patients. In one patient, latanoprost was used in both eyes, and the uveitis was bilateral. Four of five eyes had a history of prior inflammation and/or prior incisional surgery. All patients were rechallenged with the drug. RESULTS: The uveitis improved after cessation of latanoprost with or without topical corticosteroids. It recurred after rechallenging with latanoprost in all eyes. CONCLUSION: There is a possible association between latanoprost and anterior uveitis. Topical prostaglandin analogs may be relatively contraindicated in patients with a history of uveitis or prior ocular surgery. This association may also be possible in eyes that have not had previous uveitis or incisional surgery.

Administration, Topical↗
PubMed1996

Timolol hemihydrate vs timolol maleate to treat ocular hypertension and open-angle glaucoma.

PURPOSE: We compared the therapeutic efficacy and safety of timolol hemihydrate to timolol maleate in patients with ocular hypertension and chronic open-angle glaucoma. METHODS: We conducted this three-month study as a multicentered, masked, parallel group comparison. Both the 0.25% and 0.5% concentrations were evaluated against similar concentrations of timolol maleate. Dosing was twice daily. An open-label, nine-month study followed the masked portion of the protocol, in which all patients received either 0.25% or 0.5% timolol hemihydrate. A total of 371 patients were included in both the 0.25% and 0.5% studies. RESULTS: We found statistically similar intraocular pressures with both the 0.25% (18.3 and 18.6 mm Hg for the hemihydrate and maleate groups, respectively) and 0.5% (19.9 and 19.5 mm Hg for the hemihydrate and maleate groups, respectively) concentrations of timolol hemihydrate and timolol maleate after three months of masked treatment. Likewise, peak intraocular effect at two hours after taking the medication was statistically similar between medicines at both concentrations. Likewise, both ocular and systemic safety were similar between the maleate and hemihydrate preparations at both concentrations. In the nine-month open-label protocol, therapeutic efficacy (19.9 and 19.1 mm Hg for the 0.25% and 0.5% concentrations, respectively) and safety of timolol hemihydrate were similar to effect and safety of the three-month protocol. CONCLUSIONS: This study suggests that timolol hemihydrate had an ocular hypotensive efficacy and safety profile statistically equivalent to that of timolol maleate for up to three months of therapy. Timolol hemihydrate showed efficacy and safety similar to that observed within the first three months, for up to one year of therapy.

Adolescent↗
PubMed1996

Binocular function in early glaucoma.

PURPOSE: This study investigated whether certain binocular mechanisms are disrupted in early glaucoma. METHODS: Glaucoma patients, suspects, and normals were tested on a battery of psychophysical tests consisting of flicker sensitivity (5 and 34 Hz), temporal cut-off frequency (CFF), contrast sensitivity (Pelli-Robson chart), and stereoacuity. Monocular channels were evaluated with tests of monocular flicker performance and spatial contrast sensitivity. Binocular summation on spatial and temporal tests was used to reflect integrity of binocular neural interactions. Stereoacuity was taken as a measure of performance of disparity processing mechanisms. RESULTS: The groups differed in terms of binocular flicker sensitivity at both temporal rates, binocular and monocular peak contrast sensitivity, and stereoacuity. Binocular summation of both spatial and temporal sensitivity was normal. The glaucoma suspect group was distinguishable from the age-matched normal group on binocular contrast sensitivity and stereoacuity. CONCLUSIONS: The binocular mechanisms that mediate stereoacuity appear to be heavily disrupted, whereas the binocular mechanisms that mediate central neural interaction of monocular inputs are normal. Although monocular spatiotemporal abilities are disrupted, the binocular processes combine the monocular input normally. In addition, our results suggest a benefit of binocular testing for routine assessment of glaucoma patients. The profound disruption of stereoacuity appears to result from disorder in the spatial sampling array at the ganglion-cell level similar to the disorder reported in the normal periphery and the central retina of strabismic amblyopes. These and previous findings were reviewed to evaluate the supposition of preferential M-pathway disruption in early glaucoma. Such a model can not be reconciled with the present findings. We conclude that measurements of temporal modulation sensitivity fit well with such a model, but that the current evidence of spatiotemporal contrast sensitivity disruption is less supportive of such a model.

Analysis of Variance↗
PubMed1995

Prevent Blindness America visual field screening study. The Prevent Blindness America Glaucoma Advisory Committee.

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).

Adolescent↗
PubMed1994

Pharmacokinetics, acid-base balance and intraocular pressure effects of ethyloxaloylazolamide--a novel topically active carbonic anhydrase inhibitor.

Studies evaluated a novel series of biscarbonylamides of 2-amino-1,3,4-thiadiazole-5-sulfonamide (2-ATS) for topical use as ocular hypotensive carbonic anhydrase inhibitors (CAI). Transcorneal accession rate constants (k(in)) for ethyloxaloylazolamide (EtOxAz), ethylsuccinylazolamide (EtSuxAz) and ethyladipoylazolamide (EtAdipAz), and activity against carbonic anhydrase (CA) were determined in vitro by an enzymatic assay and High Performance Liquid Chromatography (HPLC). The ocular hypotensive effect was measured by pneumatonometry on conscious normotensive New Zealand White (NZW) rabbits, using masked, randomly assigned paired-eye design for treatment vs. control. At various time points following treatment, aqueous humor, ciliary processes and corneal buttons were collected and assayed for drug concentrations using enzymatic assay and HPLC. Transcorneal accession rates for the novel compounds were 1.5 to 18 times that of the parent compound, acetazolamide (Actz). The activity factor for EtOxAz was 72.8 x 10(3) hr-1 of 23 times that of Actz. The activity factors for EtSuxAz and EtAdipAz were 6.8 and 1.1 x 10(3) hr-1, respectively. Subcutaneous administration of EtOxAz. EtSuxAz, and EtAdipAz, in 225 mumol kg-1 concentrations, induced a significant decrease in the intraocular pressure (IOP) at 1 hr post injection of 4, 5.8 and 6 mmHg for EtOxAz, EtSuxAz and EtAdipAz, respectively (P < 0.05 for each). Topical application of 75 mM EtOxAz lowered the IOP by 3.0 mmHg (P < 0.05). This effect was maximal after 60 min and persisted for at least 5 hr. EtSuxAz and EtAdipAz did not alter the IOP significantly when given topically. Subcutaneous administration of the three compounds was associated with acidosis (pH as low as 7.21). Topical application did not cause any changes in the acid-base balance. There was a direct correlation between the amount of drug delivered to the ciliary process and the magnitude of ocular hypotensive effect. Following topical application EtOxAz reached the ciliary epithelium in concentrations sufficient to inhibit more than 99.95% of the ciliary carbonic anhydrase (> 8 microM), while plasma drug concentrations were below the limit of detection by the assay (< 0.2 microM). Within the first hour after topical application, half of the EtOxAz was eliminated from the anterior uvea. In summary, EtOxAz is a topically effective CAI. Structural modifications of thiadiazole sulfonamides, with the increase of both water and lipid solubilities, improved the transcorneal accession while preserving sufficient CA inhibitory activity, resulting in a significant IOP decrease following topical application of EtOxAz.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid-Base Equilibrium↗
PubMed1994

A comparison of the efficacy of various metipranolol-pilocarpine combinations in patients with ocular hypertension and primary open-angle glaucoma.

We compared the ocular hypotensive effects of four fixed-dose metipranolol-pilocarpine combinations in nineteen ocular hypertensive subjects and glaucoma patients. Each patient was tested with all of the study medications: vehicle alone, 0.1% metipranolol HCl + 2% pilocarpine HCl, 0.1% metipranolol HCl + 4% pilocarpine HCl, 0.3% metipranolol HCl + 2% pilocarpine HCl, and 0.3% metipranolol HCl + 4% pilocarpine HCl, in a single dose, randomized, double-masked, cross-over placebo-controlled trial. In addition, another eight age and baseline intraocular pressure (IOP)-matched subjects received 0.1% or 0.3% metipranolol HCl, while a similar group of 14 volunteers received 2% or 4% pilocarpine HCl. A two week washout period was instituted between the various groups of treatments. All four metipranolol-pilocarpine combinations were more effective than placebo or either medication alone in reducing the average IOP for up to 8 hours (p < 0.05 for each treatment group). Metipranolol HCl 0.3%, regardless of the pilocarpine concentration, demonstrated the most significant IOP lowering effect, reducing the IOP by 4.9 mm Hg or about 20% from baseline. However, 0.1% metipranolol HCl in combination with 4% pilocarpine HCl was found almost as effective with a 18.5% reduction in IOP from baseline, but a shorter duration of action. In conclusion, all metipranolol-pilocarpine combinations were more efficacious than either medication alone in a single-dose trial. Additional multiple-dose studies are needed to determine the long-term effectiveness and tolerance of combining 0.3% metipranolol HCl with either 2% or 4% pilocarpine HCl.

Adult↗
PubMed1994

Nasolacrimal occlusion improves the therapeutic index of antiglaucoma medications.

The purpose of this study was to assess whether nasolacrimal occlusion improves the therapeutic index of various antiglaucoma medications. Use of nasolacrimal occlusion resulted in better efficacy and safer usage. Nasolacrimal occlusion used with 2% pilocarpine, 1.5% carbachol, 0.25% timolol maleate, or 1% epinephrine every 12 hours gave the maximal response for these drugs. Applying 0.25% timolol and 1.5% carbachol every 12 hours gave the maximal response for this combination. Nasolacrimal occlusion did not alter the effect of 0.1% dipivefrin, and since the corneal penetration of this prodrug is 17 times that of epinephrine, 0.05% dipivefrin every 12 hours might be an adequate dosage for maximal effect. Our findings suggest that most of the commercially used antiglaucoma agents can achieve the same maximal effect with lower concentrations and less frequent administration (never exceeding every 12 hours). Nasolacrimal occlusion should markedly decrease systemic absorption and side effects following topical treatment.

Aged↗
PubMed1993

The efficacy of brimonidine in decreasing elevations in intraocular pressure after laser trabeculoplasty.

PURPOSE: The authors explored the empirical dosing requirement for administration of an alpha 2-adrenoceptor agonist, brimonidine, and determined its efficacy in decreasing elevations in intraocular pressure (IOP) after 360 degrees argon laser trabeculoplasty (ALT). METHODS: This vehicle-controlled, double-masked, multicenter trial evaluated three dosing regimens of brimonidine. Two hundred thirty-two patients for whom 360 degrees ALT was indicated were randomized into one of four treatment groups: 0.5% brimonidine both before and after ALT; brimonidine before but vehicle after ALT; vehicle before but brimonidine after ALT; or vehicle at both times. RESULTS: During the first 3 hours after 360 degrees ALT, the overall incidence of IOP elevations of 5 mmHg or greater was 38% (23 of 60 eyes) in the group receiving vehicle only, and it ranged from 3% to 9% (2 of 62 to 5 of 53 eyes) in the groups receiving any brimonidine treatment. There was little difference in efficacy between the three dosing regimens of brimonidine. Brimonidine was well tolerated by the patients. CONCLUSION: Based on this large, controlled, multicenter study, 0.5% brimonidine was an effective agent for reducing elevations in IOP after 360 degrees ALT. Only one dose, administered either before or after 360 degrees ALT, was required.

Adrenergic alpha-Agonists↗
PubMed1993

Topical ophthalmic beta blockers: a comparative review.

Topically administered beta blockers are the preferred medical therapy for glaucoma. These agents reduce intraocular pressure (IOP), thereby preventing damage to the optic nerve and the subsequent loss of vision. Timolol, betaxolol, levobunolol, metipranolol, and carteolol are the topical beta blockers available in the U.S. They have similar IOP-lowering efficacy, but differ in other pharmacological properties. Topically administered beta blockers are generally well tolerated. They undergo systemic absorption, however, and can adversely affect cardiovascular and bronchopulmonary function in patients with existing diseases such as heart failure, sinus bradycardia, chronic obstructive airways disease, or asthma. Betaxolol, which is beta 1-selective, and carteolol, which has intrinsic sympathomimetic activity (ISA), may have systemic tolerability profiles superior to the traditional nonselective, non-ISA beta blockers. These hypotheses require confirmation in controlled clinical trials. Local adverse effects associated with beta blockers include stinging, burning, red eye, itching, tearing and loss of corneal sensitivity. Stinging upon instillation is a particularly frequent finding with betaxolol (up to 30% to 40% of patients). Preliminary evidence suggests that carteolol has the best local tolerability profile of these drugs.

Administration, Topical↗
PubMed1993

In vitro inhibition of collagen formation by 2,4-pyridine dicarboxylate and minoxidil in rabbit corneal fibroblasts.

Two anti-fibrotic agents were evaluated in vitro for potential application in trabeculectomy. The rate of collagen formation by cultured rabbit corneal fibroblasts was determined by [3H]proline uptake and hydroxylation assay. Incubation of fibroblasts, for 96 hours, with 16 mM 2,4-pyridine dicarboxylic acid (2,4-PDCA), a competitive inhibitor of prolyl 4-hydroxylase, decreased [3H]OH-proline formation from control by 28.2 +/- 3.9%; (average +/- S.E.M), whereas 10 mM minoxidil, an antihypertensive pyrimidine oxide and a lysyl hydroxylase inhibitor, induced a decrease of 17.3 +/- 4.5%. Incubating fibroblasts with a mixture of the two inhibitors, 16 mM 2,4-PDCA and 10 mM minoxidil, resulted in a further decrease in [3H]proline incorporation of 40.7 +/- 5.1%. After 96 hours of incubation with the inhibitors, rabbit corneal fibroblast growth was decreased from control by 17.2 +/- 4.2% and 10.5 +/- 4.5% for 16 mM 2,4-PDCA and 10 mM minoxidil, respectively. These effects were dose dependent. The results suggest that both 2,4-PDCA and minoxidil have an inhibitory effect on collagen formation and may be useful in delaying surgical wound healing.

Animals↗