Reports

This report is based on medical evidence presented at sanctioned medical congress, from peer reviewed literature or opinion provided by a qualified healthcare practitioner. The consumption of the information contained within this report is intended for qualified Canadian healthcare practitioners only.

6th International Glaucoma Symposium

Athens, Greece / March 28-31, 2007

According to Prof. Anastasios Konstas, Aristotle University, Thessaloniki, Greece, “Relying on a single intraocular pressure [IOP] reading to treat glaucoma, or to establish a target pressure and choose optimum therapy, can be misleading.” He suggested that ophthalmologists should consider 24-hour pressure control in all glaucoma patients who continue to deteriorate despite apparently good pressure control based on single office readings.

All modes of therapy—medical, laser and surgical—can be helped by 24-hour pressure assessment, as this can establish key IOP characteristics, for example, peak pressure, fluctuations and mean 24-hour pressure.

“We know that a higher peak pressure may be an independent risk factor for glaucoma and that IOP measurement taken outside office hours extends the peak pressure in a high proportion of patients,” Prof. Konstas stated, pointing out that mean peak pressure during 24-hour monitoring has been reported to be almost 5 mm Hg higher than that documented during office hours (Hughes et al. J Glaucoma 2003;12(3):232-6). He suggested that 24-hour pressure assessment might become an important tool for assessing the risk of glaucomatous progression and the quality of IOP control.

Twenty-four-hour pressure monitoring can be “the acid test” in evaluating the efficacy of medical therapy. It can compare the quality of IOP control between two agents and can guide the clinical choice of initial and stepwise treatment. Optimal therapy should provide good, long-term 24-hour pressure control and minimize fluctuations in 24-hour pressure. “A 25% mean 24-hour IOP reduction from untreated baseline may realistically be the target for a successful medication,” Prof. Konstas told listeners.

Recent Study Results

He outlined the results from a recent study evaluating short-term (two months) and mid-term (six months) 24-hour pressure control of two glaucoma therapies. The study involved evening-dosed latanoprost and dorzolamide/timolol fixed combination twice daily (Ophthalmology 2007; in press). It was a prospective, randomized crossover study in 53 patients with primary open-angle glaucoma or ocular hypertension.

Twenty-four-hour IOP was measured at baseline, after two months and after six months. Both treatments effectively reduced 24-hour IOP at both two and six months, but some differences between the therapies were observed. At two months, mean 24-hour pressure control with the fixed combination was significantly better than with latanoprost. There were significant differences at two time points (10 am and 10 pm), but no difference for mean 24-hour fluctuations.

At six months, the treatments produced similar mean 24-hour pressure control (18.1 ± 1.9 mm Hg for dorzolamide/timolol fixed combination and 18.3 ± 1.9 mm Hg for latanoprost) although the fixed combination still provided better control at 10 am (-0.8 mm Hg) and 10 pm (-1.1 mm Hg). With latanoprost, IOP was further reduced at month 6 (0.3 mm Hg improvement over month 2) while IOP reduction with the combination was unchanged.

“Our study suggests that the fixed combination works quicker and remains stable, while latanoprost shows improvement over time,” Prof. Konstas told delegates. He added, “Both drugs showed narrow 24-hour pressure fluctuations at six months compared with two months. It is important to know what happens beyond six months, but it could be that chronic therapy with these agents may offer some protection against fluctuations in 24-hour pressures.” This study was the first to compare 24-hour control after six months. All previously published 24-hour IOP studies have evaluated pressure after four to eight weeks.

Prof. Konstas emphasized that it is not known which 24-hour IOP characteristic is most important in the long-term prognosis or which IOP time points are the most critical for predicting efficacy. There is still a need for robust evidence of a causal relationship between specific 24-hour IOP characteristics and glaucoma progression. In answer to a question from a delegate, he said that there are as yet no data to show that lack of IOP control at nighttime leads to disease progression when IOP during the day is on target.

Adverse events in the study were as expected. There was more hypertrichosis and ocular itching with latanoprost and more burning/stinging and bitter taste with dorzolamide/timolol fixed combination.

Researchers from Liverpool Hospital, New South Wales, Australia, compared the ocular comfort of single doses of brimonidine/timolol and dorzolamide/timolol fixed combination in 30 normal subjects. Discomfort was graded on a six-point scale after 30 to 40 seconds and again after five to six minutes. At the first measurement, 80% of testers reported the brimonidine/timolol combination to be more comfortable. However, at five minutes after instillation, there was no difference between the treatments with respect to ocular discomfort (P=0.129).

A presentation from researchers at First City Hospital, Sofia, Bulgaria, reported a comparison of dorzolamide/timolol fixed combination with latanoprost in 30 patients with open-angle glaucoma and IOP above 24 mm Hg. The fixed combination significantly reduced IOP by 4.3 mm Hg while a 3.8 mm Hg reduction in IOP was seen in the latanoprost cohort. The treatments were found to produce similar IOP reduction.

Ocular Blood Flow: Clinical Implications

Despite IOP reduction, in many patients glaucoma continues to progress. This indicates the multifactorial nature of the disease, reported Dr. Alon Harris, Indiana University School of Medicine, Indianapolis.

The etiology and progression of glaucomatous damage is not only pressure-dependent but is also related to vascular supply of the optic nerve and retina. Vascular risk factors identified in epidemiological studies include diabetes, hypertension and migraine. In addition, low diastolic perfusion pressure has been identified in several studies as the most important vascular risk factor, suggesting that ischemia has a role in the disease pathogenesis.

There is now some evidence that ocular blood flow deficits are found in glaucoma and correlate with visual field damage. “I would say we now have the first seeds of evidence that ocular blood flow is related to visual function in some patients,” Dr. Harris remarked.

Several studies have shown that carbonic anhydrase inhibitors (CAIs) can increase ocular blood flow. For example, a four-week study suggested dorzolamide/timolol fixed combination might increase blood flow while attaining similar IOP reduction to latanoprost/timolol (Siesky et al. J Ocul Pharmacol Ther 2006;22(5):353-61). Postulating that there can be limitations to the interpretation of single studies, Dr. Harris reported a new meta-analysis on the effect of topical CAIs on ocular blood flow from papers published between 1966 and 2007. Thirteen of 36 identified articles met the criteria for inclusion in the analysis. “Within these studies, we found that scanning laser ophthalmoscopy suggests that CAIs decrease arteriovenous passage time, and these reductions occur both in combined assessment of the primary retinal arteries and especially in the superior temporal quadrant of the retina,” he reported.

The meta-analysis therefore indicates that topical CAIs can improve ocular hemodynamic in addition to IOP reduction. However, more work is needed, Dr. Harris confirmed. “Maintaining objectivity under the umbrella of evidence-based medicine, we need longitudinal studies to assess the effects of ocular blood flow improvement on glaucoma.”

Visual Field Preservation

In a further discussion of ocular blood flow, Dr. Antonio Martinez, University of Santiago de Compostela, Spain, reported an evaluation of the effect of dorzolamide/timolol fixed combination on the progression of visual field damage over four years in patients with open-angle glaucoma (80 eyes). Treatment improved ocular blood flow, as measured by color Doppler imaging, and Kaplan-Meier analysis showed that the risk of progression of visual field damage was significantly lower in eyes treated with the fixed combination than in control eyes (with less visual field damage) treated with timolol alone.