"Prospective longitudinal studies indicate that imaging measurements can be predictive of future conversion to glaucomatous visual field in eyes with normal fields at baseline, but lots more work is needed to assess the ability of imaging to detect glaucomatous change over time," said Dr. Bowd, assistant research scientist, glaucoma/imaging, Hamilton Glaucoma Center, University of California, San Diego (UCSD).
The National Institutes of Health have supported several longitudinal imaging-related studies since about 2000, and several additional studies are active in other countries. Only a small number of reports have been published on detection of change over time, however.
Reasons for this occurrence include the slow progression of glaucoma, in which many years of follow-up are required to document change. Also, imaging technologies change relatively frequently and updates are not always compatible, Dr. Bowd said.
In practice, the lack of published research and the speed at which technology changes can mean that only a few years of follow-up data obtained with a particular instrument are available on a patient; this is usually insufficient time to detect change.
The Heidelberg Retina Tomograph (HRT, Heidelberg Engineering), for example, has undergone three versions since its inception in the early 1990s; fortunately, the change detection algorithms are theoretically compatible, Dr. Bowd said.
"That's not the case with the GDx scanning laser polarimeter [Carl Zeiss Meditec] and OCT [optical coherence tomography, Carl Zeiss Meditec], which have also gone through a couple of changes that are not compatible," he continued. "Therefore, with the newest versions of these instruments, we can only really look at progression for about the past 5 years.
"Also, it's difficult to identify false positives because imaging technologies may be more sensitive to change than standard techniques, and currently the criteria for significant change with imaging measurements is not well defined," Dr. Bowd said.
"In summary, for findings from progression studies, little evidence exists currently that imaging technologies can detect glaucomatous change over time. There are more reasons for this than limitations in technology, and lots more work needs to be done to assess the ability of these measurements for detecting change over time," he said.
What constitutes change?
An important consideration is determining what constitutes change, Dr. Bowd added, explaining that it can be difficult to distinguish disease-related change from long-term variability.
Dr. Bowd also noted that longitudinal studies provide information about early detection as well as progression. "A number of cross-sectional studies have claimed that imaging technologies can detect preperimetric glaucoma, which is usually defined as a glaucomatous-looking disc with normal visual fields," he said. "The problem is that lots of nonglaucomatous discs—for instance large ones and myopic ones—can appear glaucomatous cross-sectionally, and this may result in false positives leading to misclassification.
"The only way to be sure that preperimetric glaucomatous discs are truly glaucomatous is by evidence of change over time, such as change in disc appearance or conversion to glaucomatous visual fields," Dr. Bowd added.
The study design for addressing this issue is the prospective longitudinal study, and the analysis technique most used is Cox proportional hazard analysis, which considers measurements at baseline, follow-up time, and endpoint status. For instance, the endpoint can be conversion to disease, evidenced by disc change or development of abnormal visual fields in the case of patients with ocular hypertension.
The results of the analysis are expressed as a ratio-based risk of developing glaucoma given a particular baseline measurement; a hazard ratio greater than 1 indicates increased risk.