Ateam led by a researcher at the Stanford University School of Medicine demonstrating the potential of precision health. The senior author of the study said, "Analyzing fluid samples from the eye can totally change how we treat patients."  The study findings were appeared in the JCI Insight.

The team employed proteomics, the large-scale study of proteins, to identify four on-the-market drugs that successfully quelled symptoms triggered by several of the overabundant proteins. The findings, although not curative, demonstrate the potential of treating rare and complex eye conditions — and potentially other inflammatory diseases — by matching existing drugs with proteins that are abnormally expressed in the eyes of individual patients.

A team led by Mahajan identified the gene responsible for the disease in 2012; a cure has yet to be developed. In the past, clinicians treating NIV patients used a trial-and-error approach to treat each symptom as it appeared, Mahajan said.

Analyzing biopsies

Researchers performed liquid biopsies: A small amount of intraocular fluid was extracted from eight eyes of members of the same family at various stages of NIV and, as a control, four eyes with a noninflammatory eye disease. The researchers looked for 200 types of immune-signaling molecules called cytokines and identified 64 that were different, usually more abundant, in the eyes affected by NIV. In addition, they found that a protein called TNFalpha, which is usually abnormal in inflammatory conditions, was not elevated. Clinicians had previously assumed it was a culprit in NIV, yet infusions of an anti-TNFalpha drug called infliximab had not alleviated symptoms for patients with the disease. Now they know why.

The researchers worked through the symptoms of the disease, matching each one with abnormal levels of proteins from the biopsies, and then with existing drugs that could potentially provide relief.

One feature of NIV is the excessive formation of new blood vessels in the retina, which can lead to a blinding hemorrhage. Clinicians traditionally treat this type of hemorrhage with surgery. However, eye surgery prompts inflammation and scarring in NIV patients. The protein analyses revealed elevated levels of vascular endothelial growth factor, or VEGF, that correlated with moderate cases of the disease. The researchers turned to an anti-VEGF drug, bevacizumab, which had been approved to treat macular degeneration. Injections of bevacizumab were able to resolve hemorrhages in seven NIV eyes without surgery, the study said.

Drug reduces eye inflammation

The protein analysis also revealed numerous inflammatory compounds that could be treated with steroids, so the research team decided to put steroid implants into three of the NIV eyes. The researchers used this clue to solve another issue in NIV: Scar tissue grows inside the eye, causing the retina to detach from the back of the eye.

More gradual decline in eye health

Mahajan said he believes the work illustrates the power of proteomics, which could help fulfill the potential of precision health to diagnose diseases before they advance and provide a real-time look at biochemical processes driving disease.

"This is a fantastic example of the precision health approach we're taking in ophthalmology at Stanford," said Jeffrey Goldberg, MD, PhD, professor and chair of ophthalmology. "It's innovative, has broad applicability and, most importantly, is helping patients."