New Retinal Scan Analysis Can Predict Progression of Macular Degeneration within a Year

The ARVO logo

During the past several months, there has been much research interest focused on predicting the progression of age related macular degeneration (AMD). Last month, a new study in JAMA Ophthalmology investigated the pattern and progression of wet (also called neovascular) AMD and determined that having wet AMD in one eye was associated with an increased incidence and progression of AMD in the other eye.

More recently, researchers at Stanford University have derived a new computer algorithm [i.e., a step-by-step problem-solving procedure] that they say predicts, with high accuracy, whether an individual with mild or intermediate AMD will progress to the wet stage. The technique, which uses standard optical coherence tomography (OCT) testing, has “added on a computerized image-processing step that analyzes not only that OCT scan but any previous ones available from that same patient’s earlier visits,” says study author Dr. Daniel Rubin.

The Association for Research in Vision & Ophthalmology

The research, entitled Quantitative SD-OCT Imaging Biomarkers as Indicators of Age-Related Macular Degeneration Progression was published in the November 5, 2014 edition of Investigative Ophthalmology & Visual Science, the official journal of the Association for Research in Vision and Ophthalmology (ARVO). ARVO is an international organization that encourages and assists research, training, publication, and dissemination of knowledge in vision and ophthalmology, including low vision.

[Editor’s note: Spectral-domain optical coherence tomography (SD-OCT) is a type of non-contact medical imaging technology similar to ultrasound and magnetic resonance imaging (MRI). OCT uses reflected light to produce detailed cross-sectional and three-dimensional images of the eye.]

The authors are Luis de Sisternes, Noah Simon, Robert Tibshirani, Theodore Leng, and Daniel L. Rubin, who represent the following institutions: Stanford University and Stanford School of Medicine, Stanford, California, and the University of Washington, Seattle, Washington.

About Age-Related Macular Degeneration

Age-related macular degeneration (AMD) is a gradual, progressive, painless deterioration of the macula, the small sensitive area in the center of the retina that provides clear central vision. Damage to the macula impairs the central (or “detail”) vision that helps with essential everyday activities, such as reading, preparing meals, watching television, playing card and board games, and sewing.

AMD is the leading cause of vision loss for people aged 60 and older in the United States. According to the American Academy of Ophthalmology, 10-15 million individuals have AMD and about 10% of people who are affected have the “wet” type of AMD.

Wet (Neovascular) Macular Degeneration

In wet, or exudative, macular degeneration (AMD), the choroid (a part of the eye containing blood vessels that nourish the retina) begins to sprout abnormal new blood vessels that develop into a cluster under the macula, called choroidal neovascularization (neo = new; vascular = blood vessels).

Because these new blood vessels are abnormal, they tend to break, bleed, and leak fluid under the macula, causing it to lift up and pull away from its base. This damages the fragile photoreceptor cells, which sense and receive light, resulting in a rapid and severe loss of central vision.

About Dry Macular Degeneration

The dry (also called atrophic) type of AMD affects approximately 80-90% of individuals with AMD. Its cause is unknown, it tends to progress more slowly than the wet type, and there is not – as of yet – an approved treatment or cure. “Atrophy” refers to the degeneration of cells in a portion of the body; in this case, the cell degeneration occurs in the retina.

In dry age-related macular degeneration, small white or yellowish deposits, called drusen, form on the retina, in the macula, causing it to deteriorate or degenerate over time.

Photograph of a retina with drusen

A retina with drusen

Drusen are the hallmark of dry AMD. These small yellow deposits beneath the retina are a buildup of waste materials, composed of cholesterol, protein, and fats. Typically, when drusen first form, they do not cause vision loss. However, they are a risk factor for progressing to vision loss.

Risk Factors for Macular Degeneration

The primary risk factors for AMD include the following:

  1. Smoking: Current smokers have a 2-3 times higher risk for developing AMD than do people who never smoked. It’s best to avoid second-hand smoke as well.
  2. Sunlight: Ultraviolet (UV) light is not visible to the human eye, but can damage the lens and retina. Blue light waves that make the sky, or any object, appear blue, are visible to the human eye and can also damage the lens and retina. Living Well with Low Vision reports on these lighting issues in Artificial Lighting and the Blue Light Hazard. Avoid UV light and blue/violet light as much as possible by wearing sunglasses with an amber, brown, or orange tint that blocks both blue and UV light.
  3. Uncontrolled hypertension: The National Eye Institute (NEI) reports that persons with hypertension were 1.5 times more likely to develop wet macular degeneration than persons without hypertension. It’s important to keep your blood pressure controlled within normal limits.
  4. A diet high in packaged, processed food and low in fresh vegetables: NEI suggests that eating antioxidant-rich foods, such as fresh fruits and dark green leafy vegetables (kale, collard greens, and spinach) may delay the onset or reduce the severity of AMD. Eating at least one serving of fatty fish (salmon, tuna, or trout) per week may also delay the onset or reduce the severity of AMD.
  5. Race: According to NEI, Whites/Caucasians are more likely to have AMD than people of African descent.
  6. Family history: NEI reports that individuals with a parent or sibling with AMD have a 3-4 times higher risk of developing AMD.

You can read more about the full range of AMD risk factors at Risk Factors for Age-Related Macular Degeneration on the VisionAware website.

About the Research

Excerpted from Retinal-scan analysis can predict advance of macular degeneration, study finds, via Stanford Medical News:

Stanford University School of Medicine scientists have found a new way to forecast which patients with age-related macular degeneration (AMD) are likely to [progress to] the most debilitating form of the disease.

The formula distinguishes likely from unlikely progressors by analyzing patient data that’s routinely collected by ophthalmologists and optometrists when they perform retinal scans with an imaging technique called spectral domain optical coherence tomography.

This imaging technique is analogous to ultrasound. The macula is scanned with a beam of focused laser light, and the amount of reflected light coming back at each point is measured and recorded. The resulting stream of data is … converted into an extremely high-resolution, three-dimensional image.

“Right now, a patient who goes into the ophthalmologist’s office typically gets an SD-OCT scan anyway,” said the study’s senior author, Daniel Rubin, MD. “Our technique involves no new procedures in the doctor’s office — patients get the same care they’ve been getting anyway.

We’ve simply added on a computerized image-processing step that analyzes not only that scan but any previous ones available from that same patient’s earlier visits.”

From this computerized analysis, the investigators are able to generate a risk score: a number that predicts a patient’s likelihood of progressing to the wet stage within one year, three years or five years.

In the study, the Stanford team analyzed data from 2,146 scans of 330 eyes in 244 patients seen at Stanford Health Care over a five-year period. Patients were followed for as long as four years, and predictions of the model were compared with actual instances of progression to wet AMD.

The model accurately predicted every occurrence of progression to the wet stage within a year. About 40 percent of the time when the model did predict progression to wet AMD within a year, the prediction was not borne out.

“No test gets it right 100 percent of the time,” Rubin said. “You can tweak the model to trade off the risk of telling someone they will progress when they actually won’t against the risk of telling them they won’t progress when they actually will. But that’s nothing compared with the downside of a patient at high risk for progression’s not coming in soon enough.”

Rubin emphasized that this proof-of-principle study needs to be followed up by a larger study, ideally using data gathered from patients seen at other institutions. He and his associates have now embarked on such a study.

More about the Study from Investigative Ophthalmology & Visual Science

From the article abstract:

Purpose: We developed a statistical model based on quantitative characteristics of drusen to estimate the likelihood of conversion from early and intermediate age-related macular degeneration (AMD) to its advanced exudative form (AMD progression) in the short term (less than 5 years), a crucial task to enable early intervention and improve outcomes.

Methods: Image features of drusen quantifying their number, morphology [i.e., form and structure], and reflectivity properties, as well as the longitudinal evolution [i.e., development over time] in these characteristics, were automatically extracted from 2146 spectral-domain optical coherence tomography (SD-OCT) scans of 330 AMD eyes in 244 patients collected over a period of 5 years, with 36 eyes showing progression during clinical follow-up. We developed and evaluated a statistical model to predict the likelihood of progression at predetermined times using clinical and image features as predictors.

Results: Area, volume, height, and reflectivity of drusen were informative features distinguishing between progressing and nonprogressing cases. The maximum predictive performance was observed at 11 months after a patient’s first early AMD diagnosis. Those eyes predicted to progress showed a much higher progression rate than those predicted not to progress at any given time from the initial visit.

Conclusions: Our results demonstrate the potential ability of our model to identify those AMD patients at risk of progressing to exudative AMD from an early or intermediate stage.

Additional Information