It’s Nothing Personal

Our definition of glaucoma is inadequate. At a 1991 World Health Organization meeting of Collaborating Vision Centers, glaucoma was not cited on official publications as a cause of blindness, since, as one expert stated, “Glaucoma cannot be defined or treated, so it isn’t on the list.” Without a useful objective definition to lean on, specialists are instead left to diagnose glaucoma by judging characteristic optic disc and visual field changes for themselves. With about half of those with glaucoma left undiagnosed, we need better ways to both identify patients and keep them in care. An objective definition of glaucoma is vital to this goal.

There is a shortage of studies that compare how well glaucoma specialists agree on the structural features of optic nerve changes, or whether the visual field test was abnormal. Just as the US Supreme Court Justice, Potter Stewart, famously said about obscenity, many glaucoma experts feel that they “know it when they see it” (1). This amorphous approach makes it difficult to compare results across large numbers of clinical studies in glaucoma. And this challenge sparked the study that my team from the Glaucoma Center of Excellence at the Wilmer Institute in Baltimore, the Singapore National Eye Center, and the Department of Ophthalmology and Visual Sciences at Dalhousie University in Canada are currently conducting. We expect to publish the work in March/April 2020.

Despite more than 30 years of quantitative functional tests – in the form of objective visual field testing – it is only in recent years, thanks to the onset, development and improvement in optical coherence tomography (OCT), that we have been able to perform quantitative structural tests such as measuring the thickness of the nerve fiber layer. As a result of such developments, my team and I began to wonder; surely, we could find some features of OCT and visual field tests that clinicians agree represent definite glaucoma?

As it turns out, finding agreement is difficult. For some doctors, glaucoma is an acute attack of intraocular pressure of 70 mmHg with angle closure. For others, you have glaucoma if you have exfoliation syndrome, or if your pressure is sufficient to cause blurred vision. We decided to use objective damage to the optic nerve as the criterion, defining glaucoma as glaucomatous optic neuropathy (GON).

We interviewed more than 260 glaucoma specialists and asked them to define GON by the features they would expect to see. And that led to a set of structural and functional features that these specialists agreed would be a reasonable way to reach an objective definition of glaucoma. Currently, this definition is being further validated by asking doctors around the world to send us structural and functional data on eyes they consider to be “definite” GON, “possible or probable” GON, or those that simply don’t have it. We then run analyses to show that you can identify glaucoma from very standard features of the OCT and field tests, allowing standardized comparisons across research studies. Further validation studies are also planned for the future, with methods that may include the use of longitudinal databases or AI.

Based on this kind of work, it may be possible to eventually reach a consensus on how to objectively define glaucoma. An objective definition is crucial to clinical research; it ensures we are all talking about the same type of effect of this disorder on the optic nerve. Furthermore, by studying exactly what we think is and is not glaucoma, we may well see features that are currently being overlooked, purely because such large international databases aren’t being put together. During our investigations, we were surprised to see so few differences between continents in our validation study. Comparative, international studies such as these are extremely important. Although we already know there is a genetic component to glaucoma, having concrete data from such studies will provide evidence as to whether we may need to adjust our definition of glaucoma for certain groups of people, such as those from different world regions.

It is equally important to note that this definition will not be imposed on people and that it has nothing to do with enabling national governments to derive treatment reimbursement decisions. It is simply about improving clinical research in glaucoma. However, a prior definition of glaucoma by Foster and colleagues (2) ended up being cited 1,350 times in clinical research studies by 2017, comprising 10 percent of all papers in which the subject is open angle glaucoma (3). We therefore know that such consensus definitions can be useful, and that they would be used widely if people deem them reasonable.

In the future, I’d like to see glaucoma specialists putting their heads together and realizing that, whereas in the past, a doctor may have simply looked at a patient and said: “That’s glaucoma,” we are now in an era that enables us to do much better. We must ensure that, as glaucoma specialists, we are all defining this leading cause of blindness in a way that moves beyond the individual subjective opinion.