Next-level imaging puts optometry on front line of diabetes diagnosis

Emerging imaging technologies are improving evaluation, diagnosis and management of patients with diabetes and leading to earlier detection.

These next-level technologies fall into three buckets: high-resolution, expanded field fundus photography; OCT angiography; and widefield imaging.

For 25 years, ETDRS was the standard in diabetic retinopathy imaging and diagnosis, according to Primary Care Optometry News Editorial Board Member Jerome Sherman, OD, FAAO. The protocol used seven images, each of them 30 degrees, to image the back and center of the eye, but would only cover 30% of the retina, he said in an interview.

Today, with widefield imaging that can be done on nondilated pupils, a single image captures 80% of the retina, Sherman said.

OCT angiography has simplified the imaging process because it does not require a referral; eliminates the need for injection and, thus, possible reactions to dye; and saves patients money, according to PCON Editorial Board Member Julie Rodman, OD, FAAO.

“Many times, the stage of disease is underestimated,” Diana L. Shechtman, OD, FAAO, who works in a large retina practice and is a PCON Editorial Board Member, said in an interview.

“Through the use of ultra-widefield fluorescein angiography (UWFA), which captures 200 degrees of the retina, we often see a patient referred as having moderate nonproliferative diabetic retinopathy (NPDR) who is confirmed to have severe NPDR or even proliferative diabetic retinopathy,” she said. “UWFA helps in the assessment of peripheral ischemia as well as neovascularization. Because capillary nonperfusion upregulates pro-angiogenic factor through a hypoxia-induced mechanism, we find that identifying the presence of ischemia is incredibly valuable in diagnosing the stage of the disease, as well as the management of the patient.”

With high-resolution ultra-widefield imaging, the peripheral retina is visible without distortion, and lesions there correlate with nephropathy and a number of other issues associated with diabetes, Aaron Lech, OD, FAAO, told PCON.

While monitoring, diagnosis and imaging platforms are evolving, our experts still advocate for an annual dilated fundus examination for patients with diabetes.

Lech suggested that optometrists should let diagnostics drive diagnoses.

“The technology has improved, but we do a poor job in annual eye exams at leading with the diagnostics,” he said. “We can do a better job of focusing on the problems and challenges patients are having by utilizing technology to provide them with counsel on things none of us can see.”

OCT angiography

In 2014 OCT-A was introduced, but it was not intended to upstage spectral domain OCT, Rodman said; it provides a different dimension. SD-OCT provides a structural, cross-sectional look at the retina and choroid, while OCT-A provides a noninvasive look at the microvasculature of the retina and choroid, she said.

“We can use OCT in tandem with OCT-A to get a simultaneous view of structure and function,” she said.

Before OCT-A, fluorescein angiography (FA) would require a referral.

“There were a lot of wonderful things OCT-A brought to the table because optometrists can’t do FA,” Rodman added.

OCT-A uses motion contrast to assess the blood flow within the tissue, she said. It samples the same area of the retina a few times and then looks at those samples for any differences between the samples, and those differences are interpreted as blood flow.

“Although FA remains the gold standard in the evaluation of vascular perfusion, OCT-A provides a noninvasive tool to assess retinal vascularization via motion contrast imaging,” Shechtman said. “This is useful in the evaluation of retinal microvasculature disorders like diabetic retinopathy.

“For example, OCT-A can provide additional information regarding localization and morphology of intraretinal microvascular abnormalities, neovascularization of the disc or neovascularization elsewhere,” she continued. “Exquisite assessment of both the superficial and deeper capillaries allows for visualization of vascular changes related to diabetic retinopathy, such as vascular remodeling, microaneurysms and enlargement of the foveal avascular zone, thus, contributing to the assessment of both diabetic retinopathy-related complications and expanding our understanding of the pathogenesis of the disease. Of note, such findings are not easily discerned during a normal comprehensive dilated exam and, hence, its identification leads to earlier diagnosis.”

Shechtman added, “Diabetic macular ischemia is related to functional retinal damage. The diagnosis of macular ischemia becomes crucial in predicting diabetic retinopathy progression and the prognosis of current treatment.”

“Before the advent of OCT-A we were restricted to FA, which could not view the deep plexus,” Rodman said. “It could only view the superficial plexus. Studies are showing that many of the early diabetic changes that we are seeing – diabetic macular ischemia, diabetic macular edema or capillary nonperfusion – are actually happening first in the level of the deep plexus (Carnevali et al., Simonett et al.).”

FA was missing important information that would provide a preemptive look, she added. OCT-A picks up vascular changes that are occurring earlier than can be seen on funduscopic examination alone.

“You can see a patient with no clinical findings. Then you do an angiography and find all these changes on it and discover that there is a lot going on at a subclinical level that we aren’t seeing,” Rodman continued.

Microaneurysms are visible on OCT-A, as well. She said studies have shown that the amount of microaneurysms has a direct correlation to the likelihood of a patient developing diabetic macular edema (Hasegawa et al.).

Optovue just received FDA approval for its AngioAnalytics program, which provides a quantitative analysis by using numbers and color scales to display the level of ischemia and assist in the objective evaluation of what is happening at the microscopic level, she said.

Rodman added, “There’s often a lot of obscuration when reading a fluorescein angiography due to leakage from fluorescein. OCT doesn’t have that problem. There is no leakage with OCT-A. It images beautifully, with a lot of clarity.”

She runs an OCT-A on every patient with diabetes.

“It has become part of our routine examination in this population,” she said. “We recommend it as a screener in all of our diabetic patients.”

Cost can be an issue, Rodman noted.

“If you are using it appropriately, I think it pays for itself,” she said. “If I had to choose one device, it would be OCT and OCT-A right now.”

“It’s important that optometrists are open and receptive to new technology ... at the end of the day it’s making us better diagnosticians and improving patient care,” Rodman said.

Widefield imaging

Studies from the Joslin Diabetes Center in Boston (Silva et al.) suggest that if a patient has lesions predominantly in the periphery, he or she has about a fivefold increased risk of progression to proliferative diabetic retinopathy, according to Sherman.

“Something as simple as taking one image of the back of the eye with the ultra-widefield retinal imaging from Optos gives you a lot of information compared to the old standard, seven images, and I think that’s very important,” he said.

Eight years ago, Sherman started using a Daytona, the initial “next generation” ultra-widefield imaging device from Optos. The first hour or two he ran it on nine patients and picked up small, peripheral hemorrhages in two of them. Neither patient was previously diagnosed with diabetes, he said. After following up with them, they both went on to develop diabetes about a year later.

“It’s possible that the small hemorrhages developed early on and were detected even before the patients were diagnosed a year later with diabetes by an internist,” Sherman said.

He said SUNY is trying to figure out how optometrists should be imaging patients in a primary care clinic.

“Right now, we aren’t routinely doing OCTs or ultra-widefield imaging, but I’m an advocate for doing both. They are both fast and give us a tremendous amount of information,” Sherman added.

Early diagnosis is crucial, he said, and he is an advocate of ultra-widefield imaging that allows diabetes detection in fairly early stages and to monitor progression.

“From an optometrist’s point of view, we are in a position to diagnose diabetic retinopathy and treat appropriately when indicated ... but it’s an ongoing process,” Sherman said.

The identification of peripheral-related findings in diabetic retinopathy patients is associated with an increased risk of the progression of the disease, according to Shechtman.

“Patients need a full dilated exam, not just a posterior pole; that’s where widefield imaging becomes very important,” she said.

Optometry and ophthalmology are just beginning to understand how good the Optos models are for diabetes detection and monitoring, Sherman said.

“Now we have the California system (Optos) that allows for both indocyanine green and fluorescein angiography, which tells us about the integrity of the choroidal and retinal vasculature,” he said. “In the OCT world, we have OCT-A, and with improved software we can do analytics to show progression and changes over time. AngioAnalytics, which is brand new, will help us a great deal in monitoring progression.”

High-resolution, expanded field fundus photography

With high-resolution expanded field fundus photography, Lech is excited about the prospect of machine learning to detect abnormalities, via artificial intelligence. This allows optometrists to focus on the more complex cases and spend time with patients in discussion, using advanced diagnostics to confidently identify complex retinal lesions and abnormalities.

He said diagnostic capabilities in his practice are enhanced or accelerated with the use of the Clarus 500 (Carl Zeiss Meditec).

Prior to high-resolution expanded field fundus photography, it was difficult to get a clear, magnified view of the peripheral retina, “where we know that there are lesions that correlate with nephropathy and a number of other issues and complications surrounding diabetes,” Lech said. “Now you have a piece of technology where you take two snapshots and expand your view on the screen to perform a detailed analysis.”

Another unique advantage to this technology is that the images render accurately across the entire fundus, he said.

“These aren’t recreated images, using certain colors,” Lech said. “You have a full-spectrum LED light source, not just one wavelength of green or red. You’re seeing real, true color in full spectrum,” not virtual images.

“OCT is very good at data registration, data points and telling you whether an image is good enough to compare. But the images aren’t widefield ... yet,” he added.

Lech often takes a 6-mm by 6-mm segment from OCT-A and overlays it on a widefield image.

“You can get a true high-resolution image of the macula with the same technology, a high-resolution peripheral and central retina photo. You can enlarge it, and the vessels from the Zeiss Cirrus OCT AngioPlex image can be registered to the vessels in the photo and you can toggle and bring up the angiography to look at changes within the vessels.”

He uses this technique to visualize foveal vascular changes.

In the big picture of diabetes management, “you’re starting to manage prediabetics, to see things at the retinal vascular level that are precursors to an actual diagnosis of diabetes,” Lech said.

This technology helps providers take a proactive approach, and combining the technologies allows Lech to be on the cutting edge of detection and management.

“Practically speaking, this technology is clinically available and has day-to-day use,” he said. “With the new ultra-widefield technology, you not only have retinal photography capability for wide peripheral lesions in diabetics, but you can get the same image of the optic nerve for glaucoma management or even anterior segment photography.”

Lech runs ultra-widefield imaging on every patient so he can identify diabetic patients when they are prediabetic.

He also recommends a diagnostic data management system to harness all the data from the imaging systems, and functional diagnostic testing, not just static files of a photo. His office uses Forum (Zeiss), which overlays OCT and fundus photography and even combines these with visual field analysis.

“I needed interoperability,” Lech said. “I want to be able to take a photo and an OCT over multiple visits and segment out different layers, and if I can do that out of a single data management solution, that is really helpful. I’m not toggling with four screens. I’m able to layer elements to show what’s on the surface versus what’s lurking in the shadows. That sort of capability is really nice and gives me a keen sense of what’s going on today and predicting future risk.”

Lech added that this method works for all four doctors in his practice, who represent a wide range of generations and serve a variety of patient needs.

Ultra-widefield is a “no-brainer” in an office of two or more doctors, he said, and “there’s no way you can’t make this profitable.”

Diabetes counseling

Another important silo in diabetes education is patient counseling. Sherman said that optometrists should be involved in the care of the whole patient and at the forefront, “in counseling patients in order to get them to recognize the risks present in their lifestyles.”

He believes he has that responsibility.

He highlighted an example of a patient who came in for reading glasses at the age of 45 years. The patient’s retina was fine, but he was 150 pounds overweight.

“I wouldn’t be able to let that patient out of the exam room without discussing diet and how important exercise is,” Sherman said. “You can’t get everyone to change their lifestyle, but it is helpful, to some extent, to discuss it.”

Most diabetic patients have type 2 diabetes, which is preventable, he said. A patient who is 150 pounds overweight and has bariatric surgery may be able to reverse the diabetes.

“Half of the patients treated with weight loss surgery wind up not having diabetes a year after surgery (Singh et al.),” Sherman said.

“If we can prevent or delay diabetes, diabetic retinopathy to prevent blindness and diabetic nephropathy to prevent kidney failure, we can impact the economic toll of diabetes on the health care system,” he concluded.

• References:
• Carnevali A, et al. Acta Diabetol. 2017;doi:10.1007/s00592-017-0996-8.
• Hasegawa N, et al. Invest Ophthalmol Vis Sci. 2016; doi:10.1167/iovs.15-18782
• Silva PS, et al. Ophthalmology. 2013 doi:10.1016/j.ophtha.2013.05.004.
• Simonett JM, et al. Acta Ophthalmol. 2017;doi:10.1111/aos.13404.
• Singh AK, et al. Indian J Endocrinol Metab. 2015;doi:10.4103/2230-8210.163113.

• For more information:
• Aaron Lech, OD, FAAO, practices at ClearVue Eye Care in Roseville, Calif. He can be reached at: drlech@clearvue.org.
• Julie Rodman, OD, FAAO, is a professor at Nova Southeastern University College of Optometry. She can be reached at: rjulie@nova.edu.
• Diana L. Shechtman, OD, FAAO, is the consultative optometric physician at Retina Macula Specialists of Miami. She can be reached at: dianashe@comcast.net.
• Jerome Sherman, OD, FAAO, is a Distinguished Teaching Professor at the SUNY College of Optometry and in private practice at Omni Eye Surgery in New York. He can be reached at: j.sherman@sunyopt.edu.

Disclosures: Lech reported he is an advisory board member for Allergan and Carl Zeiss Meditec. Rodman reported no relevant financial disclosures. Shechtman has received lecture honoraria or served on the advisory boards or speakers bureaus for: Alcon, Allergan, Bausch + Lomb, Genentech, Regeneron, ScienceBased Health, ZeaVision and Zeiss. Sherman has lectured for Optovue and Innova.