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6th International Glaucoma Symposium

Athens, Greece / March 28-31, 2007

Dr. Keith Barton, Moorfields Eye Hospital, London, UK, summed up the challenge of treating glaucoma. “Different treatment would be needed for different stages of glaucoma because patients with glaucoma progress at very different rates and turn up at clinic at very different stages of their disease. How aggressively do we treat and when do we treat, as opposed to just watching?”

The objective of glaucoma treatment is to prevent further optic nerve damage and visual loss, with management decisions based on stage of disease, rate of disease progression, and age. Mild disease may not need treatment unless the patient’s risk-factor profile shows otherwise or actual progression is demonstrated, explained Dr. Barton. However, he confirmed that advanced disease requires aggressive treatment, unless life expectancy is short. “In advanced disease, it is probably more difficult to stop the process. It may be that structurally, the optic nerve becomes less able to support the continued survival of axons, irrespective of the pressure. More aggressive treatment may be required to prevent progression.”

First-line Strategies

Prostaglandin (PG) analogues are now commonly used as first-line treatment. Beta blockers have largely been relegated to second line because of their effect on pulmonary function, indicated Dr. Barton, emphasizing that airway obstruction increases with age. “The healthy newly-diagnosed glaucoma patient aged 50 or 60 is not only progressing along the hypothetical glaucoma continuum but is also slowly losing pulmonary function.”

Compared with other ocular hypotensives, PG analogues are not associated with systemic effects. They can produce local side effects, but these are largely not serious, “and we are all aware of these and know when to modify our patients’ treatments,” he told the audience. These agents also have the convenience of a once-a-day administration, which has an important bearing on compliance.

PG analogues are more effective than older treatments, according to French registry data reported by Gisela Kobelt, PhD, European Health Economics, Spéracèdes, France. Data were collected on 568 patients receiving treatment with latanoprost (alone or in a fixed combination with timolol), bimatoprost or travoprost. After two years, mean intraocular pressure (IOP) had decreased from 21.2 mm Hg at baseline to 16.1 mm Hg (compared with 18 mm Hg in a 1995 study from the same centre). Outcomes from this interim analysis were similar in the three groups.

Fixed Combination Treatment

Combination therapy is used in patients not reaching IOP target on monotherapy. The European guidelines recommend use of a fixed combination whenever possible to minimize the number of drops and dosing frequency to facilitate compliance. “Patient compliance is a major issue in glaucoma therapy,” indicated Prof. Norbert Pfeiffer, Director, University Eye Clinic, Mainz University, Germany. The number of agents and the time required for treatment are important factors. For example, to obtain the full effect of therapy, patients should ideally leave five minutes between drops to prevent the second drop washing out the first medication. “But very few patients do this. They just don’t have the time to wait,” Prof. Pfeiffer remarked.

The fixed combination (FC) of latanoprost and timolol (FC-LTTM) provides up to 2.5 mm Hg greater reduction in mean IOP compared with latanoprost alone, and when given in the evening, the fixed combination produces equivalent IOP-lowering efficacy to the unfixed components.

According to Prof. Pfeiffer, fixed combinations of glaucoma treatments appear to have the same efficacy as unfixed combinations with the advantage of enhanced compliance. He added, “In clinical practice, in the long term, this should give us better efficacy and a better prognosis for the patient.”

Optimal Dosing Time

There have been conflicting data from clinical studies comparing fixed and unfixed latanoprost and timolol. “Originally, we gave the fixed combination in the morning and now we know that that is not a good idea,” Prof. Pfeiffer noted. The initial study compared LTTM given in the morning with an unfixed combination of latanoprost once daily in the evening and timolol twice daily. The IOP reduction was 1.1 mm Hg greater with the unfixed combination. However, when the study was repeated, this time giving the LTTM in the evening, there was no statistical difference in mean diurnal IOP reduction (Diestelhorst et al. Ophthalmology 2006; 113:70-6). The FC provided an effective and well-tolerated alternative.

Prof. Pfeiffer offered an explanation for the improved night time efficacy of FC-LTTM. “We know that the PG analogue is more active during the day and the night if it is given at night, but we do not know why this is so. I assume the activity of the enzymes that degrade PG is lower at night so the drug will stay longer in the eye.”

Glaucoma treatment is usually initiated with monotherapy but Dr. Yelda B. Ozkurt, Department of Ophthalmology, Kartal Training and Research Hospital, Istanbul, Turkey, and colleagues presented data from a study of the use of FC-LTTM as first-line therapy in 28 patients with IOP above 30 mm Hg. Treatment reduced IOP by around 43% in a short period of time. The researchers emphasized that the study was only preliminary but indicated, “We think this could be a potent and effective first-line therapy.”

Assessing Risks in Ocular Hypertension

Ophthalmologists are following the example of general practitioners in learning how to estimate disease risk for an individual patient. Risk calculators are commonly used to quantify a person’s total cardiovascular risk and a similar validated system is now available to assess glaucoma risk in patients presenting with ocular hypertension.

Prof. Stefano Miglior, University of Milan-Bicocca, Italy, confirmed the importance of individualizing the risk of progression to glaucoma and functional impairment. “Ocular hypertension occurs in around 4 to 8% of the population over the age of 40. We really don’t know how to deal with these patients. Should they be treated or just followed up?” The dilemma is that although ocular hypertension is the most important risk factor for glaucoma, two major trials—the Ocular Hypertension Treatment Study and the European Glaucoma Prevention Study—showed that a proportion of patients, around 10 to 15%, will develop glaucoma over the next five years.

Reducing IOP is the only proven strategy for primary open-angle glaucoma or ocular hypertension. But since glaucomatous damage can progress even in patients with IOP within the normal range, ophthalmologists are evaluating other factors that might play a part in pathogenesis.

In a crossover study involving 18 patients, Dr. Carlos Figueiredo, Hospital do Olho Rio Preto, São Paulo, Brazil, and co-investigators found pulsatile ocular blood flow to be increased by both latanoprost monotherapy and a combination of dorzolamide/timolol, with the PG analogue exhibiting a greater effect (3.6 vs. 2.2 µL/min increase). Further studies are needed to establish whether enhancement of choroidal blood flow can prevent glaucoma progression.

Summary

When taking into account the many risk factors associated with glaucoma management and its long-term nature, the choice of treatment becomes important. PG analogues are considered first-line treatment. Speakers here confirmed that fixed-combination alternatives offer both improved efficacy and compliance for those patients whose disease progresses and requires add-on therapy.