Jimmy D. Bartlett

Contrast sensitivity improves after brimonidine therapy in primary open angle glaucoma: a case for neuroprotection.

Aims: To determine the visual outcome following initiation of brimonidine therapy in glaucoma. Methods: 16 newly diagnosed previously untreated glaucoma patients were randomly assigned to either timolol 0.5% or brimonidine 0.2%. Visual acuity, contrast sensitivity (CS), visual fields, intraocular pressure (IOP), blood pressure, and heart rate were evaluated at baseline and after 3 months. Results: IOP reduction was similar for both groups (p<0.05). Brimonidine improved CS; in the right eye at 6 and 12 cpd (p = 0.043, p = 0.017); in the left eye at 3 and 12 cpd (p = 0.044, p = 0.046). Timolol reduced CS at 18 cpd in the right eye (p = 0.041). There was no change in any other measured parameters. Conclusion: Glaucoma patients exhibit improved CS on initiation of brimonidine therapy.

Effects of loteprednol/tobramycin versus dexamethasone/tobramycin on intraocular pressure in healthy volunteers.

Purpose: To compare the steroid-induced intraocular pressure (IOP) and other ocular adverse effects of loteprednol etabonate 0.5% and tobramycin 0.3% ophthalmic suspension with those of dexamethasone 0.1% and tobramycin 0.3% ophthalmic suspension. Methods: Three hundred six healthy volunteers received either loteprednol etabonate/tobramycin (n = 156) or dexamethasone/tobramycin (n = 150) at 4-hour intervals 4 times a day in both eyes for 28 days in this randomized, double-masked, multicenter, parallel-group trial. IOP, visual acuity (VA), and ocular health were assessed at all study visits (days 1, 3, 8, 15, 22, and 29), whereas undilated direct ophthalmoscopy was completed at the baseline and final visits. Adverse events (AEs) were assessed at all follow-up visits. Results: The number of subjects experiencing IOP increases of ≥10 mm Hg from baseline at any study visit for the loteprednol etabonate/tobramycin group (3 subjects, 1.95%) was significantly lower than that for the dexamethasone/tobramycin group (11 subjects, 7.48%; P = 0.0280), as were mean changes from baseline IOP (P < 0.05 at all visits). The lowest VA recorded for any subject at any visit was 20/40 and reductions of ≥2 lines at any visit were observed in 14 (4.55%) eyes for loteprednol etabonate/tobramycin and in 23 (7.82%) eyes for dexamethasone/tobramycin (P = 0.1257). Both treatments were well tolerated. Conclusions: Loteprednol/tobramycin was significantly less likely to produce elevations in IOP than was dexamethasone/tobramycin in healthy subjects treated for 28 days. Both loteprednol etabonate/tobramycin and dexamethasone/tobramycin were well tolerated with low risks for systemic AEs and ocular AEs other than elevation in IOP for dexamethasone/tobramycin.

Spectral content of the intraocular pressure pulse wave: glaucoma patients versus normal subjects.

AbstractBackground. Many studies have found that the intraocular pressure (IOP) is lower in glaucomatous populations than in normal groups. An alternative method of analysis, commonly used in the investigation of arterial blood pressure, is to reduce the pulse waveform to its component Fourier parts. The purpose of this study, therefore, was to determine whether such a technique is applicable to the IOP pulse and to investigate whether it was superior at differentiating diseased from healthy eyes. Methods. Using a pneumatonometer, continuous 10-s IOP recordings were taken from 10 glaucoma patients and 10 normal subjects. The IOP recordings were then analysed using the fast Fourier transform (FFT) to determine their spectral components. In addition, standard IOP parameters (pulse amplitude, pulse volume, and pulsatile ocular blood flow) were measured to allow comparison with the waveform analysis technique. Results. Analysis by FFT successfully determined the IOP pulses higher spectral components up to the fourth harmonic. In addition, although standard measurements of the IOP pulse (such as pulse amplitude) were insignificant, the second (P=0.034), third (P=0.015) and fourth (P=0.013) harmonics of the waveform successfully differentiated between the glaucoma and normal groups. Conclusion. Spectral analysis of the IOP pulse appears to be a promising technique in the investigation of ocular vascular disease.

A Tolerability Study of Pirenzepine Ophthalmic Gel in Myopic Children

PURPOSE The objective of this study was to determine the safety and tolerability of pirenzepine ophthalmic gel (PIR) and the magnitude of mydriatic and accommodative effects in myopic children. METHODS This was a placebo-controlled, parallel double-masked study of unequal (4:1) randomization. Children were randomized to receive 0.5% PIR, b.i.d., or vehicle (placebo) for one week, then titrated to 1% PIR for one week, then 2% PIR for two weeks, and then for an additional 11 months. Enrolled were 26 normal healthy children, 9-12 years old, with myopia (-0.75 to -3 D) and minimal astigmatism (< or =1 D, O.U.). RESULTS Three of the 26 subjects (all in PIR group) did not complete one year of the study: one child at day 8 who inadvertently received 2.0% PIR as the first concentration, due to accommodative insufficiency, one child for follicular conjunctivitis at 9 months, and one child for administrative reasons at month 1. Other than the child discontinued at day 8, all patients were titrated up to the highest concentration of PIR evaluated. When measured 1 hour after instillation of PIR 0.5%, there was a mean mydriatic effect of less than 1 mm compared to vehicle in either bright or dim light. With increasing concentrations of PIR, this effect became numerically larger, although still remained less than 1 mm in either bright or dim light. Measured approximately 12 hours after instillation, there was little mydriasis within each group (relative to baseline) or between treatments. Similar mild PIR effects were seen on accommodative amplitude. In general, the adverse events reported were mild or moderate in severity, resolved rapidly, and were of the nature and incidence to be expected in a study of a topical anti-muscarinic gel in children of this age. CONCLUSION The promising efficacy results and acceptable safety profile justifies proceeding with additional clinical trials to evaluate efficacy and further characterize the safety of pirenzepine in a larger patient population.

Hypercapnia invokes an acute loss of contrast sensitivity in untreated glaucoma patients

BACKGROUND/AIM It is widely accepted that hypercapnia results in increased retinal, choroidal, and retrobulbar blood flow. Reports of a visual response to hypercapnia appear mixed, with normal subjects exhibiting reduced temporal contrast sensitivity in some studies, while glaucoma patients demonstrate mid-peripheral visual field improvements in others. This suggests that under hypercapnic conditions a balance exists between the beneficial effects of improved ocular blood flow and some other factor such as induced metabolic stress; the outcome may be influenced by the disease process. The aim of this study was to evaluate the contrast sensitivity response of untreated glaucoma patients and normal subjects during mild hypercapnia. METHODS 10 previously untreated glaucoma patients and 10 control subjects were evaluated for contrast sensitivity and intraocular pressure while breathing room air and then again during mild hypercapnia. RESULTS During room air breathing, compared with normal subjects, glaucoma patients had higher IOP (p = 0.0003) and lower contrast sensitivity at 3 cycles/degree (cpd) (p = 0.001). Mild hypercapnia caused a significant fall in contrast sensitivity at 6, 12, and 18 cpd (p < 0.05), only in the glaucoma group. CONCLUSION Glaucoma patients with early disease exhibit central vision deficits as shown by contrast sensitivity testing at 3 cpd. Hypercapnia induces further contrast loss through a range of spatial frequencies (6–18 cpd) which may be predictive of further neuronal damage due to glaucoma.

Tolerability of loteprednol/tobramycin versus dexamethasone/tobramycin in healthy volunteers: results of a 4-week, randomized, double-masked, parallel-group study.

ABSTRACT Objective: To compare the ocular comfort and tolerability of loteprednol etabonate 0.5%/tobramycin 0.3% (LE/T; Zylet*) with dexamethasone 0.1%/tobramycin 0.3% (DM/T; TobraDex†) in healthy volunteers. * Zylet is a registered trademark of Bausch &Lomb, Inc., Tampa FL, USA † TobraDex is a registered trademark of Alcon Laboratories, Inc., Fort Worth, TX, USA Research design and methods: In this multicenter, randomized, double-masked, parallel-group study, healthy volunteers (n = 306) were randomized to receive LE/T or DM/T four times per day for 28 days. Subjects recorded subjective ratings for seven comfort/tolerability parameters using an electronic patient diary (EPD). The primary endpoint was the difference at week 4 from the ratings of an artificial tear at baseline in comfort/tolerability parameters between treatment groups, using a noninferiority paradigm. Clinical trials registration: ClinicalTrials.gov, NCT 00532961. Results: The 97.5% confidence intervals for the lower bound were within –10 for all of the seven comfort/tolerability parameters evaluated (pain, stinging/burning, irritation, itchiness, foreign-body sensation, dryness, and light sensitivity). Secondary analysis revealed small but significant within-treatment differences in pain favoring LE/T over tears and in light sensitivity favoring tears over DM/T (p < 0.01). Small between-treatment differences in the changes from baseline tear ratings to individual study visits favored LE/T for pain, stinging/burning, irritation, itchiness, foreign-body sensation, and light sensitivity at visit 4 (p ≤ 0.04); for pain, stinging/burning, and foreign-body sensation at visit 5 (p ≤ 0.03), and for dryness and light sensitivity at visit 6 (p ≤ 0.05). Conclusions: LE/T satisfied all conditions of noninferi-ority to DM/T in comfort and tolerability. Subjects receiving LE/T were more likely to report better ocular comfort/tolerability ratings relative to baseline artificial tears than subjects receiving DM/T. Limitations: The study population consisted of healthy volunteers.

Latanoprost-Induced Stabilization of Central Visual Function in Patients with Primary Open-Angle Glaucoma

PURPOSE Previous studies have demonstrated that visual function as measured by contrast sensitivity (CS) improves in primary open-angle glaucoma (POAG) patients following beta-blocker therapy and trabeculoplasty. There is evidence that ocular hypotensive agents, such as latanoprost, may provide benefit in terms of improved visual function, despite relatively small differences in the ocular hypotensive effect, when compared to other drugs. The aim of this study was to prospectively compare the effects of latanoprost and timolol maleate in Gelrite on CS. METHODS Twenty (20) POAG patients on a monotherapy treatment regimen of topical beta blockade and with clinically stable intraocular pressure (IOP) were recruited for this single-masked, randomized, crossover study. Subjects were randomized to begin treatment with latanoprost 0.005% once-daily in the evening or timolol maleate 0.5% in Gelrite once-daily in the morning. At the end of a 3-month treatment period, each subject was crossed over to receive the alternative treatment for 3 months. Blood pressure, heart rate, IOP, and CS were assessed at baseline and after 4, 12, 16, and 24 weeks of treatment. Static central contrast sensitivity was evaluated at four spatial frequencies, 3, 6, 12, and 18 cycles/degree. Visual-field sensitivity was evaluated by using a commercially available program. Static threshold visual-field sensitivity was assessed at baseline and after 12 and 24 weeks of treatment. RESULTS Subjects who were treated for 3 months with latanoprost, after being switched from timolol, experienced an improvement in CS at 3 cpd (P = 0.03). Conversely, subjects who were treated for 3 months with timolol, after being switched from latanoprost, demonstrated a significant loss in CS at 3 cpd (P = 0.04) and at 18 cpd (P = 0.03). Changes in CS occurred without a corresponding change in IOP, since there were no between-group differences (P > 0.05) at the end of each treatment phase. CONCLUSIONS Compared with timolol maleate in Gelrite, latanoprost appears to significantly improve, or at least maintain, central visual function, as measured by CS, at different spatial frequencies in patients with POAG.