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A NEW ERA FOR RETINAL DIAGNOSTICS

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Posted: Thursday, December 11, 2014

The recently published EURETINA guidelines (Schmidt-Erfurth et al, BJO 2014; 98: 1144-1167) provide comprehensive recommendations for the diagnosis and management of neovascular age-related macular degeneration (AMD). This includes a comprehensive discussion of diagnostic procedures, including fluorescein angiography, autofluorescence imaging and optical coherence tomography (OCT).

“Retinology and vitreoretinal surgery are some of the most exciting fields in medicine. The progress in these sub-specialties in the last few years has been immense, particularly in the treatment of macular degeneration, venous occlusion, diabetic retinopathy and inflammation. Therefore it is necessary to establish a catalogue of guidelines and recommendations to help the ophthalmologist provide the best treatments for patients,” Gisbert Richard MD, founding president of EURETINA, told EuroTimes.

But science does not live in a vacuum, noted Dr Richard, Chairman of the Department of Ophthalmology, University Eye Clinic Hamburg-Eppendorf, Germany. Costly new treatments come at a time when health care systems are under enormous pressure to economise. The advice from an international independent society like EURETINA has an important role to play not only in determining the best treatment, but also in reimbursement decisions.

The EURETINA guidelines remind clinicians that fluorescein angiography continues to be the first step in confirming a suspected case of AMD. Angiography is still considered the primary basis for clinical classification and initiation of therapy.

The guidelines also note that fluorescein angiography may still prove useful for monitoring anti-VEGF therapy in patients with high myopia, extrafoveal lesions and in cases of fresh choroidal neovascularization (CNV) reactivation at the borders of a fibrotic lesion. Fluorescein angiography and indocyanine green angiography are also recommended when there is sudden worsening of clinical symptoms, haemorrhage or pigment epithelial detachment.

Fluorescein angiography is a tried and true tool in ophthalmology, but it is not without potential problems. It is invasive and can be uncomfortable for patients. Adverse effects, although rare, include nausea, hives, hypotension and anaphylaxis.

A new approach, high-speed swept-source OCT angiography could eliminate those risks, while providing additional diagnostic information. David Huang MD, PhD and colleagues at the Casey Eye Institute, Oregon Health & Science University, Portland, US, have reported promising results in imaging the optic nerve head and CNV with this technique.

Besides avoiding systemic complications that can occur with conventional angiography, OCT offers the advantages of three-dimensional imaging, and allowing separation of disc, retinal and choroidal circulations. It can distinguish CNV above or below the retinal pigment epithelium.

It can also provide sections and projections along any plane. Current disadvantages include a small field of view, but this is expected to improve with higher speed scanning. Also, while OCT angiography can visualise fluid space and retinal thickening, it does not provide visualisation of leakage.

“OCT angiography can distinguish normal retinal circulation in the inner retinal layer, CNV in the outer retinal layer, and choroidal circulation,” he told EuroTimes, adding that he can foresee a time when the initial fluorescein angiography would be replaced completely by OCT angiography.

Dr Huang’s team has begun recruiting patients for an NIH-supported study (PI: Yali Jia and Steven Bailey) using high-speed OCT angiography in AMD. The primary goals of the OCT Angiography in Neovascular Age-Related Macular Degeneration study are to use OCT angiography to diagnose the presence of abnormal new blood vessels and to evaluate patients undergoing treatment for CNV.

The study also seeks to determine if reduced flow to the choroid is a risk factor for developing wet AMD. “OCT angiography is able to quantify CNV area which appears to be a leading indicator for the reduction and re-emergence of CNV after anti-VEGF treatment. So monitoring of CNV OCT angiography may provide more timely treatment strategies, compared to relying on visualisation of fluid accumulation on structural OCT, or assessing changes in visual acuity,” said Dr Huang.

However, for the time being, fluorescein angiography will remain the first step in the diagnosis of macular degeneration. Once angiography confirms a diagnosis of AMD, diabetic macular oedema (DME) or other retinal disease, clinicians rely on OCT to monitor the disease. OCT has become the mainstay in monitoring retinal disease, favoured for its ability to non-invasively visualise optical structures instantly at high resolution.

Since it first appeared some 20 years ago following work by James Fujimoto PhD, David Huang, Carmen Puliafito MD and colleagues, OCT has evolved rapidly, with ongoing improvements in scanning speed, sensitivity and resolution.

OCT relies on low-coherence interferometry and tomography to generate high-resolution images of ocular structures. The first commercially available OCT systems were time domain based.

This was followed by the development of Fourier-domain OCT, which could be either based on a spectrometer (spectral-domain OCT) or a rapidly tuned laser (swept-source OCT). Fourier-domain OCT systems now available for clinical use can provide high-speed retina scanning with complete coverage of macular area and the creation of 3D retinal images.

Indeed, with OCT imaging widely available, and awareness of importance value of prompt treatment with anti-VEGF agents, retina specialists now advocate a ‘zero tolerance’ attitude of close monitoring with OCT and prompt therapeutic response.

With so many systems available, which tool is useful for what application? The EURETINA guidelines suggest monitoring disease activity with spectral domain OCT on a monthly basis or whenever administering anti-VEGF treatments.

 

Role of Swept-Source OCT

Swept-source OCT is generating a lot of excitement among retina specialists, but the debate continues on how best to use it. This was the subject of a discussion at the annual meeting of the American Society of Retina Specialists in San Diego recently.

“The difference between time domain and spectral domain was huge, but the difference between spectral and swept-source is much smaller. You get better visualisation of deep structures with spectral domain, it is faster, and you can look at more tissue in the same amount of time.

“Once we have more FDA approved devices on the market, swept-source makes sense. Do you go out and throw away your spectral domain machine? No, because it is such a functional technology with a good track record and normative data,” commented Alex Hunyor MD, Director of Vitreoretinal Services at the Australian School of Advanced Medicine, Macquarie University, Sydney, Australia.

“Spectral-domain OCT is perfectly adequate for treating some of the things we are treating. However, swept-source OCT does provide much better choroidal visualisation, faster speed, and better quality images,” concurred Nadia Waheed MD, Assistant Professor of Ophthalmology, Tufts University School of Medicine, Boston, US.

She added that there is not enough data out there at present on the optimal clinical applications of swept-source OCT. She noted that swept-source might find an important place in
OCT angiography.

“We have been able to obtain excellent OCT angiography images with both spectral and swept-source OCT systems. The 840nm wavelength spectral OCT appears to provide better retinal vascular details, while the 1050nm wavelength swept-source OCT provides more consistent visualisation of central retinal vessels in the optic nerve head. But there is no essential difference for clinical applications,” said David Huang.

Carmen Puliafito, currently Dean of the School of Medicine at the University of Southern California in Los Angeles, was a pioneer in the development of OCT imaging in ophthalmology. He expressed a wait-and-see viewpoint
on swept-source OCT for general
clinical use.

“The way to evaluate OCT is a clinical decision-making tool. We were pretty good with the OCT that was built at Tufts in 1992. The Stratus wasn’t bad, and current systems are great. So as a clinical decision-making tool we are really doing very well with what we have. When we are asking research oriented questions in patients with retinal degeneration, and asking why doesn’t this patient see better, then having higher resolution really does make sense. However, swept-source is a buzzword, and it not at all clear that this is the thing that will enable OCT in the future,” he said.

OCT imaging technology is evolving rapidly. Most systems now available include multiple capabilities. Newer capabilities include fundus autofluorescence, enhanced depth imaging, ultra-wide field imaging and en face OCT. Future systems will likely employ adaptive optics to further enhance imaging.

Perhaps one of the most visually interesting developments in OCT has to be full-room 3D OCT. Szilard Kiss MD and colleagues at Weill Cornell Medical College in New York are developing an imaging system that would let clinicians and researchers walk around inside the virtual retinal vasculature.

They have combined OCT imaging with volumetric reconstruction within a computer assisted virtual environment (CAVE). The viewer enters a 12 x 12ft (3.6m x 3.6m) space, and dons special 3D glasses to view 3D retinal images projected in high resolution on three walls and the floor of the room. While this system is not likely to become mainstream anytime soon, the researchers believe it could be very useful for surgical planning, and for training young surgeons.

 

Home Monitoring

Even as device companies roll out better and more expensive OCT imaging tools, efforts are also under way to develop portable affordable monitoring systems, some of which are now being used for home monitoring retinal disease.

One such device, the Foresee Home device, was evaluated in the Home Monitoring of the Eye (HOME) study, a collaborative effort from investigators of the AREDS2 study.

After in-office training, patients self administer the preferential hyperacuity perimetry (PHP) test, in which stimuli are successively flashed in various locations of the visual field. The patients identify waves or distortions on the screen and that information is transferred to a central server for analysis. Any abnormality triggers an alert, which is forwarded to the patient’s doctor.

The HOME study results, reported at the 14th EURETINA Congress in London by Usha Chakravarthy MD, Professor of Ophthalmology and Vision Sciences, Queen’s University Belfast, Northern Ireland, showed that the device did help detect CNV in high-risk patients at better levels of vision compared to standard care methods.

“This approach is clearly useful for home monitoring of persons at high risk of developing neovascular AMD,” she told EuroTimes.

The FORESEE home testing device is intended for use by almost any patient diagnosed with intermediate AMD. The device requires patients to have stable fixation, visual acuity of 20/60 or better, and functional cognitive and physical ability.

 

iMacula

The number of useful monitoring apps for patients and doctors with smartphones and tablets continues to increase. On the home monitoring front, the SightBook app from DigiSight Technologies gives retina patients many options for home vision testing.

The tests include Snellen visual acuity, Amsler grid, contrast sensitivity, colour discrimination and low light acuity
and contrast.

Patients can work with their physicians to plan a sequence of tests that can be performed on a regular schedule. These results are stored on a server that is available to the patient and the physician. The system issues an alert to the designated physician in the event of any significant change in the test results.

Another home monitoring system, myVisionTrack, developed by the Vital Art and Science company, recently became the first retina screening app to receive US FDA approval. Available only by prescription, the app is designed to have patients with degenerative eye disease regularly self test with a proprietary shape discrimination test.

The results are stored online and compared with previous test results. As with other systems, the physician is alerted in the event of any sudden change in vision.

This system is expected to be employed for monitoring patients during clinical trials.

 

David Huang: davidhuang@alum.mit.edu

Alex Hunyor: aphunyor@retina.com.au

Nadia Waheed:
nwaheed@tuftsmedicalcenter.org

Carmen Puliafito: cpuliafito@usc.edu

Usha Chakravarthy:
u.chakravarthy@qub.ac.uk

Szilard Kiss: szk7001@med.cornell.edu