Visitors to ARVO 2011 could take advantage of new insights from the front lines of research on comparisons of topical therapies. Included were studies on tolerance, effects on intraocular pressure (IOP) and whether therapy in one eye can affect the untreated fellow eye.

Papers also delivered fresh perspectives on IOP measurements, including the possible repeatability of diurnal IOP and the ocular hypotensive efficacy of Rho kinase inhibitors. Finally, the conference was steeped heavily in helpful reports on imaging and evaluation of the retinal nerve fiber layer.

How Good is Generic Prostaglandin?
The first prostaglandin analogue (PGA) to go generic was Xalatan (latanoprost, Pfizer), and patients have wondered if it will be as effective as the brand-name agent.

Researchers compared the therapeutic equivalence of Galaxia, a new formulation of generic latanoprost, to that Xalatan in lowering intraocular pressure in primary open-angle glaucoma (POAG) or ocular hypertensive (OHT) patients.219/A515

The phase III, multicenter, prospective, randomized, double-blind, parallel-group clinical trial compared the generic latanoprost with Xalatan in 185 primary open angle glaucoma (POAG) or ocular hypertension (OHT) patients who had an IOP greater than 21mm Hg at randomized visits. Patients were instructed to instill one drop in the affected eye(s) every evening at 8:00 p.m. for 12 weeks. The primary efficacy endpoint was change in IOP (mean of three assessments) from baseline after 12 weeks of treatment.

The mean difference in the reduction achieved with the two treatments was 0.1mm Hg and its confidence interval fell within the interval set for therapeutic equivalence. Both treatments were equally well tolerated. Only one patient in each treatment group withdrew because of an adverse event. This study demonstrated that the generic latanoprost and Xalatan lower IOP with equal effectiveness.

Prostaglandins and the Fellow Eye
For years, we have known about the crossover effect of beta-blockers, but this hadn’t been reported for prostaglandin analogues (PGAs) until now.

Investigators evaluated if a PGA treatment in one eye affected the IOP of the untreated fellow eye.221/A517 Between 2004 and 2009, a total of 259 patients with suspected normal tension glaucoma underwent 24-hour diurnal IOP phasing. Thirty of these patients were subsequently put on a unilateral trial with a PGA, and a diurnal IOP recording during waking hours was carried out after six weeks.

To study the contralateral effect of the PGA, the researchers compared IOP recordings of the untreated fellow eye obtained during the day-long diurnal to IOP readings at similar time points of the 24-hour diurnal phasing. The researchers concluded that, in glaucoma patients, treatment with unilateral PGA significantly reduced IOP in the untreated fellow eye.

Adverse Effects of Topical Therapy
The adverse effects of BAK have been well documented. When patients have been switched from preserved latanoprost to unpreserved timolol to avoid these effects, no changes in IOP have been found. One study assessed the improvement of ocular tolerance after three months of unpreserved timolol 0.1% treatment without significant change in IOP control in patients who were initially treated and stabilized on latanoprost monotherapy.227/A523

In a randomized, multi-center, phase IV study involving parallel-groups, researchers evaluated 150 patients with POAG or OHT who showed signs of local intolerance to latanoprost. Group one received one drop of unpreserved timolol 0.1% once daily in the morning. Group two received one drop of latanoprost once daily in the evening for 84 days. The response to treatment was defined as a combination of effect on IOP and tolerance. The researchers concluded that unpreserved timolol 0.1% maintained efficacy and also reduced signs and symptoms considerably in almost all glaucomatous and OHT patients who experienced signs of intolerance when taking latanoprost. This finding suggests that the use of unpreserved timolol 0.1% could improve patients’ compliance. Hopefully this new modality will become available to us soon.

Another study compared the IOP reduction profiles of patients taking (bimatoprost 0.03%, Allergan) nightly to those receiving Lumigan every other night.234/A530 The patients had POAG and pseudoexfoliation glaucoma (PXFG). The retrospective chart review focused on 68 eyes of 45 consecutive patients who were switched from administration nightly to administration every other night because of intolerable conjunctival hyperemia.

Every other night dosing of bimatoprost was found to effectively control IOP in the patients with POAG and PXFG who had troublesome side effects when following a daily bimatoprost 0.03% regimen. The every other night regimen may be considered an alternative to daily treatment. More research needs to confirm this study, but a significant cost savings could result if this finding is confirmed.

Corticosteroid Nasal Spray
Up to 35% of the general population and up to 90% of patients with POAG are corticosteroid responders. However, topical corticosteroids are the most effective treatments for millions of adults with allergic and non-allergic rhinitis in North America. Studies evaluating the effect of nasal steroids in glaucoma patients have been limited. With these factors in mind, researchers evaluated the effect of six weeks of nasal steroids on OHT or controlled POAG patients with or without rhinitis.213/A509

A total of 19 consecutive consenting subjects completed the study––nine in the corticosteroid arm and 10 in the placebo arm. No statistically significant differences were found between the groups in baseline characteristics, IOP at each study visit or change in IOP from baseline at any time point. At six weeks, the change in mean IOP from baseline was +0.50 ± 1.52mm Hg vs. +0.70 ± 1.44mm Hg in the corticosteroid and saline nasal spray groups, respectively. Ocular hypertensives and POAG subjects showed no evidence of IOP elevation following six weeks use of beclomethasone nasal spray (Beconase AQ). This suggests that we may not need to be as “gun shy” with the use of corticosteroids as we have been in the past.

Glaucoma Drugs and the Tear Film
A study evaluated the tear film osmolarity in patients who were treated with IOP-lowering medications.218/A514 A total of 40 consecutively recruited patients treated for glaucoma or OHT were asked to complete an evaluation of ocular surface disease symptoms. They also underwent a complete evaluation of the ocular surface, including tear film osmolarity, Schirmer test, tear film breakup time and corneal and conjunctival staining.

Researchers found that tear film osmolarity was increased in the patients, particularly in those using multiple preserved eye drops. The evaluation of the ocular surface of patients treated for glaucoma or OHT may benefit from such analysis. Future trials for new IOP-lowering eye drops should include evaluations of tear film osmolarity.

Rho Kinase Lowers IOP
A very interesting new target area for pressure lowering is showing great promise. Investigators studied the efficacy and safety of a Rho kinase inhibitor, K-115, at various concentrations (placebo, 0.1%, 0.2% and 0.4%) in patients with POAG or OHT.220/A516 In this prospective, randomized, multicenter, double-masked clinical study, 210 patients with POAG or OH were evaluated. Following an appropriate washout period that varied according to previous medication, patients received either K-115 or placebo b.i.d. at 9:00 a.m. and 9:00 p.m. for eight weeks.

IOP was measured at hospitals once every two weeks at 9:00 a.m., 11:00 a.m. and 5:00 p.m. K-115 was found to statistically significantly lower IOP in patients with POAG and OH at each point tested, indicating that it had the potential to be a new agent for glaucoma to control 24-hour IOP through twice-daily dosing.

Repeatability of Diurnal IOP
A study was performed to evaluate how a single-day IOP curve characterizes diurnal IOP parameters on future days.660/A603 Researchers considered key parameters of diurnal testing, such as mean, peak and range of IOP. Thirty-six healthy subjects underwent Goldmann tonometry at 8:00 a.m., 10:00 a.m., 12:00 p.m., 2:00 p.m., 4:00 p.m. and 6:00 p.m. on the first day and at one week, four weeks, 24 weeks and 52 weeks. Mean, peak and range of IOP were determined at each of the five visits.

Mean IOP and peak IOP, determined by single-day diurnal IOP evaluation, correlated modestly with mean and peak IOP on subsequent days. Intraocular pressure range determined by single-day IOP evaluation correlated poorly with IOP range on subsequent days. Single-day diurnal IOP assessment may not fully characterize clinically relevant diurnal IOP parameters in healthy subjects.

Choroidal Thickness in Glaucoma
Recent studies show a differing choroidal thickness with age and in patients with central serous chorioretinopathy, accompanied by a potentially varying frequency of glaucoma. The aim of one study was to assess the choroidal thickness as a measure of the blood flow to the optic nerve in patients with POAG.3501/A47

Enhanced depth imaging optical coherence tomography (OCT) was obtained in patients with established diagnoses of POAG (group 1) and an age-matched healthy control group (group 2) using the Heidelberg Spectralis spectral domain OCT (SD-OCT). Retrospective analysis and comparison of the choroidal thickness was measured. Additional assessed parameters included age, gender, overall mean RNFL thickness, BCVA, refraction, lens status and cup-to-disk ratio. Also, disease duration and glaucomatous therapy were documented.

Choroidal thickness seemed to be lower in glaucoma patients compared to healthy controls. These findings could possibly support the theory that reduced blood flow could be a contributing factor in patients with glaucoma.

Decreased Retrobulbar Blood Flow
The measure of retrobulbar blood flow may become a standard in glaucoma management. Researchers examined the relationship between retrobulbar blood flow and visual field progression in patients with POAG.3503/A49 An analysis was conducted on 73 patients with POAG who completed two years of follow-up in the Indianapolis Glaucoma Progression Study. Retrobulbar blood flow was assessed by color Doppler imaging in the ophthalmic artery, central retinal artery, temporal and nasal short posterior ciliary arteries, measuring peak systolic and end diastolic blood flow velocities and vascular resistance.

Visual field mean deviation defect, pattern standard deviation defect and calculated advanced glaucoma intervention score, as measured by Humphrey Visual Field Analyzer using the 24-2 SITA standard algorithm, were used. Stepwise model selection procedures were employed to evaluate blood flow parameters for predicting changes in visual field outcomes, based on color Doppler imaging. The researchers found that a long-term decrease in the retrobulbar blood flow may be predictive of glaucomatous deterioration in the visual field in patients with POAG.

In an observational cross-sectional study of 200 healthy patients, peripapillary normal retinal nerve fiber layer (RNFL) was determined with SD-OCT. 210/A506 Study analysis focused on one randomly selected eye per subject.

The study population (age range: 9 to 86 years) was comprised of 34% (68/200) male subjects, 67.5% whites, 13.5% African-Americans, 6.5% Hispanics, 9% Asians and 3.5% other races. Mean RNFL thickness was 94.1µm for all subjects. The thickest RNFL was noted in the inferior quadrant, followed by the superior, nasal and temporal quadrants. Thinner RNFL measurements were associated with older age and white race. There was no significant difference in RNFL thickness based on gender. SD-OCT analysis of RNFL in normal subjects demonstrated results similar to what had been found in the literature with time-domain OCT.