In a study of eye fluid from 38 patients, Johns Hopkins Medicine researchers say they have found that levels of a specific protein appear to help accurately predict whether people with the wet form of age-related macular degeneration may need lifelong, frequent eye injections to preserve vision or if they can be safely weaned off the treatments.
The researchers say the protein could also be targeted by new therapies to halt vision loss among patients with the disorder, caused by abnormal growth of blood vessels that leak fluid or bleed into the portion of the retina needed for central vision Overall, age-related macular degeneration is the most common cause of vision loss among people age 50 and older, affecting an estimated 7.3 million individuals in the United States. Standard treatment of wet age-related macular degeneration requires monthly or twice-monthly eye injections of so-called anti-VEGF drugs that slow or stop the growth of leaky blood vessels and, in most cases, stave off further vision loss. Because the injections are inconvenient, costly, uncomfortable, and carry risk of infection, retinal detachment and other side effects, Sodhi’s research team has long been studying ways to identify subgroups of patients who can safely reduce or even cease eye injection therapies without further vision loss.
For the current study, Sodhi’s team investigated whether measurable levels of certain proteins in the eye could be used as predictors, known as biomarkers, of disease stabilization or progression despite treatment. First, the team collected samples of eye fluid from 38 patients at the beginning of their treatment for macular degeneration at the Wilmer Eye Institute between 2013 and 2020 in two Maryland locations. These patients were then grouped based on the frequency with which they required treatment at the end of one year.The researchers then screened the samples of each of these groups for proteins linked to the development of abnormal blood vessels. Among the proteins present, the researchers found that one, named angiopoietin-like 4, was present at higher levels in patients who required monthly treatment when compared with patients who were eventually able to reduce the frequency of injections or even stop treatment without further vision loss. Using statistical models, Sodhi’s team found that relatively higher levels of angiopoietin-like 4 (higher than 4.22 ng/mL) accurately predicted actual clinical outcomes in the patient population, identifying with 91% sensitivity those patients who would continue to require monthly eye injections to preserve their vision
However, they found that measuring only angiopoietin-like 4 led to many false-positives, with one third of the patients flagged by the test not requiring monthly therapy. In a bid to improve the accuracy of the prediction model, they paired measurements of angiopoietin-like 4 with VEGF, the protein specifically targeted by current wet macular degeneration treatments. With both of these proteins, the researchers were able to correctly identify with 76% sensitivity and 85% specificity patients who likely need monthly eye injections; this group of wet macular degeneration patients could benefit from newer longer acting anti-VEGF therapies.In animal experiments, the researchers next examined whether blocking angiopoietin-like 4 in the eye could be a potential therapeutic approach for wet age-related macular degeneration.
The researchers used nanoparticles developed in collaboration with Jordan Green, Ph.D., Professor of Biomedical Engineering at the Johns Hopkins University School of Medicine, to deliver RNA interference (RNAi) designed to target the expression of either angiopoietin-like 4 or VEGF in the retina in mice with eye lesions similar those in patients with wet age-related macular degeneration. Mice that received either the angiopoietin-like 4-blocking RNAi treatment or the VEGF-blocking RNAi treatment, both had lower levels of abnormal blood vessel growth than mice which received control treatment. However, in mice that received RNAi targeting both VEGF and angiopoietin-like 4, the treatment showed an additive effect, with even lower abnormal blood vessel growth than RNAi targeting either protein alone.
Source: This news is originally published by news-medical.net