GLAUCOMA RESEARCH

There is a compelling need to incorporate more quality of life data in glaucoma research and to move beyond using intraocular pressure (IOP) as the only significant endpoint in observational clinical trials, according to Norbert Pfeiffer MD. “IOP is a very poor endpoint for glaucoma studies and we use it primarily because it is straightforward and simple and we can obtain it very easily. Visual fields are subjective and cumbersome and optic disc progression is an extremely difficult endpoint for observational studies. Our own studies show that glaucoma affects quality of life and we need to see more account taken of quality of life in observational glaucoma studies going forward,” he said. “Quality of life may be affected by visual loss but also by side effects of treatment such as ocular surface disease.”

Addressing delegates attending the 2013 Congress of the European Society of Ophthalmology, Prof Pfeiffer, head, Department of Ophthalmology, Johannes Gutenberg University, Mainz, Germany, said that because long-term observation studies are difficult to achieve, there may be increasing scope for model simulations based on real data to be used in the future. “The problem is that you need to observe many patients for a very long time, and we estimated it would ideally need to be about 20 years. So if you start a study now and want to have the results in 10 years, by the time you have the results nobody is interested because the medications are perhaps no longer available or other new treatments are on the market,” he said.

Reviewing the endpoints used in major observational studies conducted to date, Prof Pfeiffer noted that it was perhaps not surprising that IOP was so frequently cited. “This is because the other end points that relate to visual function are so difficult to look at and take such a long time. Two older studies from Jay and Allen and Jay and Murdoch reported that the estimated progression from detectable to end stage of primary open angle glaucoma if treatment is optimal was 38 years. This becomes 10 years in the case of unsatisfactory treatment and 3.6 years if left untreated,” he said.

Two more recent observational studies, the Early Manifest Glaucoma Trial (EMGT) and the Collaborative Initial Glaucoma Treatment Study (CIGTS), looked at visual field progress in glaucoma patients, said Prof Pfeiffer. In the EMGT, the loss over five years in mean deviation was a mean of 3.9 decibels if untreated and 2.2 decibels if treated. The data for CIGTS showed a loss of 0.3 decibels in medically treated eyes and zero in surgically treated eyes.

“The point is that glaucoma progresses very slowly, and if we look at a group of patients for just five years we may find nothing or just a tiny little bit of difference in that time-frame,” said Prof Pfeiffer. He added that other observational trials with non-IOP endpoints had also underscored the difficulty of using visual field and optic disc progression as viable endpoints in observational studies. This is where quality of life metrics can play an important role, said Prof Pfeiffer. “The recognised glaucoma guidelines state that we should look at the visual function and related quality of life, because this is important for the patient who, of course, does not know about his optic disc and visual field and will usually not pick up early change,” he said.

In terms of quality of life studies and glaucoma treatments, Prof Pfeiffer said that it was possible to derive significant information from well-designed studies. He cited a recent multicentre open-label study of 158 patients in Finland, Sweden and Germany which set out to determine if Latanoprost or the preservative-free Tafluprost was better tolerated. After 12 weeks of treatment with Latanoprost, the patients who switched to Tafluprost experienced reduced ocular symptoms such as irritation, burning, stinging, foreign body sensation and dry eye sensation.

“We can look at aspects of quality of life for these studies and learn more about our treatments just by asking patients,” said Prof Pfeiffer.

To measure specific signs of quality of life, Prof Pfeiffer cited the health utility index (HUI3), a questionnaire focusing on general health that allows comparison between different diseases, or a more specific vision-related questionnaire such as the National Eye Institute 25-item Visual Function Questionnaire (NEI-VQF-25) looking at global vision rating, difficulties with near vision, distance vision, social function, levels of independence, general mental health, driving and limitations for peripheral and colour vision and also ocular pain.

Prof Pfeiffer noted that such questionnaires could be used effectively in assessing treatments. He cited a longterm quality of life study of 154 patients which his own team conducted and which showed for the first time that the mean health utility index related very well to the visual field. The questionnaires are also useful in identifying the domains most affected by the loss in quality of life, he said.