A Great Ocean of Truth Lay Undiscovered

Famously, Sir Issac Newton wrote in 1676 that, If I have seen further it is by standing on the shoulders of giants. As clinicians and scientists we are especially familiar with the various forms of this refrain. Both clinical continuing education and scientific publishing require claims of progress to be bolstered not only by evidence but also with a historical context drawn from a vast record of peer-reviewed literature. It is through this process that we witness the pace of discovery in human health (and glaucoma research). Often this pace is incremental, but is occasionally boosted by giant steps. We also witness episodes when this parade of progress appears to be marching in circles, revisiting what once seemed to be such familiar, well-trodden turf. This is not to imply lack of direction. On the contrary, there are times when our conceptual framework requires retrofitting in order to bear the expansion promised by new discoveries, technologies, insights, and capabilities.

In this 2008 OVS Feature Issue on glaucoma, there is evidence that we are in the midst of a retrofit, looking backward in order to move forward. For example, this Feature Issue contains four papers on tonometry, the measurement of intraocular pressure (IOP), something that once seemed simple to measure and interpret. Suffice to say here that there is more to tonometry than what meets the eye.

At first glance, it also seemed that the results of several recent large scale randomized clinical trials had finally provided irrefutable evidence confirming that IOP lowering treatment is effective for reducing the rates of glaucoma development and progression. With this evidence in hand, we could now march forward confidently - needing only to find those individuals at risk for glaucoma, initiate their IOP lowering therapy, and monitor them for progression. Sounds simple. In this issue, Dr. Balwantray Chauhan carefully examines some of the highest impact clinical trials and asks us to consider several important caveats before we move forward in an effort to treat every patient at risk for glaucoma. Dr. Harry Quigley also examines published studies that underscore one of the most important reasons why prescribed IOP lowering treatments frequently fail to prevent glaucoma progression: poor adherence. Dr. Quigley describes ongoing studies that further address the problem and suggests possible solutions.

Monitoring the utility of glaucoma treatment necessarily requires the ability to determine whether the disease process has progressed. In this issue, Dr. Paul Artes describes how challenging it can be to both define progression and to reliably determine whether it has occurred. He outlines sound, practical strategies that we can employ now for both patient care and research, as well as where he thinks future work on progression may lead. Dr. Artes reiterates how important it will be to reconcile our outcome measures with those most meaningful to patients. In this regard it is interesting to consider the study presented by Dr. Alex Black and colleagues about the effects of glaucomatous visual field loss on postural stability.

In his 2006 Prentice Award Lecture and paper in this issue, Dr. Ronald Harwerth harkens back a century to the ideas of Ramón y Cajal as he constructs a framework for his recent and ongoing research on the relationship between structural alterations and functional consequences of glaucomatous neuropathy. Dr. Harwerth credits Cajal's essential ideas in helping to form both the hypothesis driving this work and the title of his paper: A Neuron Doctrine for Glaucoma. Also in this issue, Drs. Christopher Bowd and Michael Goldbaum have thoroughly reviewed the topic of machine learning classifiers as applied to glaucoma, which highlights the utility of new analytical techniques in the extraction of diagnostic information from combinations of measures of structure and function.

Research continues in the quest for better measures of both the structural and functional consequences of glaucoma. For example, in this 2008 Feature issue, we find a pair of papers on two alternative measures of visual system function for glaucoma assessment, both being objective measures, which might avoid well-known problems of variability associated with psychophysical measures such as standard perimetry. Professor Michael Bach and Dr. Michael Hoffman provide an update on the pattern electroretinogram (PERG), while Professor Harry Wyatt and colleagues present data for their implementation of pupil perimetery, another objective technique that may be suitable for rapid glaucoma screening. This issue also includes new research into the quantification of retinal nerve fiber layer (RNFL) structural change due to glaucoma. Specifically, Dr. Pinakin Gunvant and co-workers have re-visit scanning laser polarimetry (SLP), a technique that has received a great deal of attention in the last decade or so. Numerous studies have shown SLP to be an effective glaucoma diagnostic and, more recently, that SLP measurements may even predict future glaucomatous loss. However, SLP provides atypical results for a substantial portion of the population, and this potentially complicates diagnostic interpretation in those eyes. Dr. Pinakin Gunvant and co-workers have conducted a study whose aim was to determine whether shape-based analyses of SLP results would be diagnostically effective in eyes with atypical SLP results.

Once glaucoma is diagnosed, it requires treatment. To this end, there are several active streams of novel therapeutic approaches under investigation. In this issue, Drs. Francesca Cordiero and Adriana DiPolo and colleagues have reviewed recent work on neuroprotection from their own and other laboratories. Collectively, their work demonstrates numerous examples of how inter-disciplinary collaboration serves to hasten the pace of discovery in each field. Another excellent example of inter-disciplinary collaboration leading to novel observations and breakthroughs comes from Drs. Crawford Downs, Michael Roberts, and Claude Burgoyne, who have reviewed theirs' and other recent work on biomechanical aspects of the optic nerve head and peripapillary sclera. Here we see a synthesis of ideas and methods, each existing separately in glaucoma research and biomedical engineering, which now propel each beyond previous limitations.

There is no doubt that we still have a very long way to go before eliminating glaucoma as the second leading cause of worldwide blindness. Yet the papers in this 2008 OVS Feature Issue on Glaucoma represent a sample of the many talented and dedicated individuals who work diligently toward that larger goal, uncovering one important discovery at a time, in carefully planned and directed increments - even if it sometimes means revisiting what once seemed like familiar ground.

Newton also wrote, I do not know what I may appear to the world, but to myself I seem to have been only like a boy playing on the sea-shore, and diverting myself in now and then finding a smoother pebble or a prettier shell than ordinary, while the great ocean of truth lay all undiscovered before me.

We hope you will find the articles in this issue to be informative, stimulating, and to contain a few choice pebbles that might inspire a diversion of your own into the ocean of truth that remains undiscovered.

Brad Fortune

Portland, Oregon

Allison M. McKendrick

Melbourne, Australia

William A. Hare

Irvine, California

Robert N. Weinreb

San Diego, California