An eye for diagnosing disease

Instruments designed by visual neuroscientist Professor Ted Maddess have helped to diagnose glaucoma in millions of people around the world. Now a new device could transform the detection and management of patients with other serious eye diseases – and, possibly, neurological disorders.

One long-standing method of investigating suspected glaucoma – and of screening for the disease – is to test peripheral (side) vision with a machine called a standard automated perimeter. (Glaucoma mainly affects the periphery of the visual field.)

The perimeter checks for blank spots, with patients pressing a button each time they see a little white dot, corresponding to a pinprick of light.  

While the standard instrument is still widely used, two more advanced devices – underpinned by innovative technology developed by Maddess, and marketed by Carl Zeiss Meditec, the world's biggest supplier of visual instruments – have boosted the diagnostic armoury of ophthalmologists.

The more recent version, the FDT (Frequency Doubling Technology) Matrix Perimeter, was released in 2003. Producing more consistent results than the traditional perimeter, it is also faster at evaluating patients with substantial eye damage, testing each eye in six minutes rather than eight or nine.

The Matrix, moreover, assesses 95 per cent of the peripheral visual field, compared with 0.05 per cent tested by the older machines.

Together with its forerunner, the FDT Perimeter, launched in 1997 and still in use, the Matrix has swallowed up about one-tenth of the perimetry market, achieving gross sales of at least US$350 million to date.

Until the latter of two patents filed by Maddess lapsed this year, the ANU received royalties of two per cent.

The FDT technology has generated more than 600 academic papers, and is preferred by many patients, according to Maddess, who is based at the Eccles Institute for Neuroscience in the John Curtin School of Medical Research.

Not only is it quicker for the majority of glaucoma patients – those already diagnosed, who are being monitored to gauge the effectiveness of treatment – but the stimuli are larger and more visible.

"With the standard perimeters, they feel like they're missing some of the stimuli, and they find that annoying and even frightening," says Maddess.

The two FDT devices produce more consistent results than the older machines. No need for an uncomfortable chin rest either; patients rest their forehead on a visor and look into a tube.

Even more promising is Maddess's latest invention, which has been ten years in development and represents a quantum leap forward from the FDT perimeters.

Now at an advanced prototype stage, the nuCoria Visual Field Analyser – nuCoria is the ANU start-up company commercialising the technology – delivers 22 stimuli per second to both eyes concurrently.

It takes just six minutes to appraise both eyes – or 80 seconds, with an alternative test which screens fewer, larger regions of the peripheral visual field.

And, rather than patients pushing a button, a video screen records the tiny movements of their pupils as they respond to different stimuli. Those responses, representing neural  activity, are then measured to create a visual field map.

"It's an objective test, which means you can probably test a wider range of people, including younger and disabled people," says Maddess, who received the Clunies-Ross Award in 2002 for devising and commercialising the FDT technology. "It also eliminates the problem of malingerers."

Developed in collaboration with Maddess's colleague Dr Andrew James, a statistical mathematician, the nuCoria instrument is based on a technology called multifocal pupillographic objective perimetery.

Tested in a clinical setting by ophthalmologists from Canberra Hospital – who see patients at the Institute's consulting and treatment rooms, and have also trialled it at the hospital – the new machine has proved even more accurate than the Matrix at diagnosing glaucoma.

It has also, to the surprise of its creators, demonstrated rich potential for the diagnosis and management of the two biggest sources of blindness in Western countries: diabetic retinopathy, an eye disease affecting many diabetes patients, and macular degeneration, which occurs in the elderly. (Glaucoma is the third biggest source.)

Studies suggest that the device – already the subject of 18 peer-reviewed papers, with more in the pipeline – is more efficient than the standard or FDT perimeter at detecting those diseases in their early stages.

In some cases, that could mean patients being treated earlier and more effectively.

"You're talking about serious diseases that affect very large numbers of people worldwide, especially given the scourge of diabetes which is expanding every day," says Maddess, who is also director of the ARC Centre of Excellence in Vision Science.

"Our device would be a step up in glaucoma management, but it could transform retinal disease detection. We're not quite sure why yet, but it's unbelievably good at detecting these diseases. There's just nothing else that compares with it at the moment."

Early indications are that the nuCoria, currently being tested by major opthalmic companies, could also help with the diagnosis and management of certain neurological diseases, particularly multiple sclerosis, epilepsy and migraine.

MS, in particular, is characterised by a delayed response to neural stimuli, which the new technology, unlike its predecessors, can pick up and assess.

A study with MS patients found a correlation between the length of that delay and the degree of disability – something not detected by expensive MRI machines, which are generally used to track the progression of the disease.

"If you can test more cheaply, you could give the test a little more often, and that might allow you to manage the disease in a more nuanced way," says Maddess.

With epilepsy, the device can detect a seizure within the past week or fortnight. It can also distinguish between the two main forms of epilepsy – generalised and focal ­– and gauge the effects of a recent migraine.

Retinal damage caused by diabetes corresponds with a delayed reaction to stimuli, too. Used before and after treatment given to reverse the damage, the new instrument could help clinicians determine whether drugs are working.

The machine can measure the strength of the brain's response to stimuli, and map the distribution of eye damage.

In glaucoma – which is also investigated through a pressure test and optical nerve examination – damaged cells typically form an arc shape. In macular degeneration, they sit in the middle of the visual field. After a stroke, the left or right half of both eyes is impacted.

While there is limited treatment for some eye diseases, monitoring their progress can yield important insights.

"People with diabetes can be counselled that 'your eyes are in trouble, you need to get more serious about your glycaemic control'," says Maddess.

"Or with macular generation, they can be told to stop smoking, which is the number one risk factor, or to take certain vitamins which have been shown to work quite well."

With the nuCoria technology covered by six patents, a sale or licencing deal could bring substantial royalties for the ANU, particularly if the company succeeds in expanding into the larger neurological market.

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