Early Detection of Diabetes Comes Through the Eyes

A new review suggests that patients be screened for signs of diabetes at the optometrist

With Gloria Wu MD and Kathryn Richdale OD Phd

Many patients see their optometrist more than any other medical professional. A new review explains how these appointments can be used to spot signs of diabetes and prediabetes.

By the time most eye care professionals see a diabetic with eye problems, it has progressed to diabetic retinopathy. Sometimes, the eye diagnosis precedes a diabetes diagnosis because patients are more likely to see an optometrist than a primary care physician. But a new review has summarized a group of potentially early tells on the ocular surface that eye doctors can look for, perhaps even before metabolic disease takes hold and eye impacts are reversible.

Symptoms

In the review, Kathryn Richdale, OD, PhD of the University of Houston and her team point to changes in four areas:

  • cornea
  • conjunctiva
  • eyelids
  • tear system

The cornea shows the most changes, and the authors noted a list that included:

  • an increase in corneal thickness
  • corneal cell density reduction which leads to changes in cell density and shape
  • increased corneal auto-fluorescence 
  • increased corneal stiffness 
  • changes in corneal nerve length, density, and branching
  • corneal sensitivity to pressure, temperature, and chemicals is reduced 
  • an increase in dendritic cell density
  • multiple types of epithelial cell changes.

Many of the changes are exacerbated by the increase in time a patient has diabetes. Some are also found in patients who are prediabetic or even simply obese. “Although the early effects of obesity or prediabetes on corneal health have not been well explored,” the authors state, “given the continuum of diseases seen in other aspects of the body, it is likely that the structure and function of the entire cornea is altered before the diagnosis of diabetes.”

Dry eyes, including decreased tear production and changes in tear breakup time are common. Doctors may also see dilation of the large conjunctival vessels and a decrease in diameter of the smaller capillary vessels. Tear composition can also exhibit changes, among them are differences in glucose levels, which can lead to changes in microbial composition in the eye – different types and larger bacterial load.

Diagnosis

In all of these cases, tests for these changes can be accomplished without invasive means, although most optometrist and even ophthalmologic practices are not set up to do all of this kind of testing.

Some of these same changes are seen in other diseases, says Richdale, such as dry eyes occurring in thyroid disorders, or even just because of contact use. “But we know these subtle changes are happening, so we want to find in-office tests that are not invasive.”

Richdale recalls cases where patients come in to see her already suffering from irreversible eye damage. They sometimes don’t have a primary care physician, let alone an endocrinologist. “They don’t know they have diabetes,” she says.

The most promising potential comes in testing for corneal nerve changes.  “Gold standard is a punch biopsy,” she explains, which can be painful and costly, and there can be issues with healing afterwards. “But our paper shows peripheral neuropathy to nerves in the cornea can be observable with imaging – and that with diet and exercise can be improved. We can find that out a lot less invasively.”

Having a compendium of the kinds of changes that are readily visible to a doctor looking for them could help establish better criteria for a provider when doing an eye exam. Doctors need to know more about research on the front of the eye, she says, so they can get better at making appropriate referrals earlier. “The goal is to continue research and figure out which of these tests are the best for predicting diabetes, and then improve the specificity of them.”

Currently, the results of any one of these might point to early diabetes, or it could point to something else, Richdale says. “The next step is to get funding to see which tests are the most specific to diabetes. Some are subtle, and we need to find the best signal in that noise.”

One potential might be a tear biomarker, she says. There is already a product on the market that looks for a specific protein for a type of dry eye, and perhaps researchers could create a similar product used for a marker specific to metabolic disease.

“I don’t know if patients know that by looking at your eyes we can tell a lot about systemic health,” Richdale says. “We can tell about high blood pressure or cholesterol looking at the veins in your eyes, and not invasively.”

Smartphone photos capture signs of diabetes for telehealth appointments

Patients themselves may be able to help eye doctors with these kinds of tests. After diabetes is active, there are changes in the eye related to dryness that can be seen with a simple snap of a smart phone camera, says Gloria Wu, MD, an ophthalmologist in San Jose and a clinical instructor at UC San Francisco. She is presenting a poster at the virtual ENDO-2020 in June that found a simple photo of the inside of your eyelid can show changes in the meibomian glands which grow greater in poorly controlled diabetes.

Wu and her colleagues conducted a chart review of 120 patients diagnosed with dry eye who had infrared imaging studies done. They found the loss of meibomian glands was associated with elevated HbA1c.

While this study was based on infrared photos, Wu says sending a black and white photo from a smartphone of the inside of the eyelid to an ophthalmologist can be enough for that doctor to tell if blood sugar is not under control. Such virtual methods of testing might be more valuable as people continue to shelter in place. “This is the first time we have looked at dry eye and diabetes and found this relationship,” she says.

While most doctors are aware that diabetes can change the retina, Wu says that most don’t know that with a smart phone picture, they can see this kind of change. As Richdale says, there are other diseases which cause dry eye, but Wu notes that in conjunction with lab tests, these photographs can be additional information for physicians to help determine whether glucose is well-controlled – or simply to alert a patient that they need to go get a blood sugar test from their doctor because they may have diabetes.

Not every ophthalmologist is open to using a picture sent over the internet as a diagnostic tool, Wu notes. And not every endocrinologist is in touch with all of the research on diabetes and changes in the eye.

“Diabetes is extremely complex, it impacts every organ system, and a lot of people are very sick when they come to see us,” she says. “This is another way of helping patients manage it.”

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