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Retinopathy of Prematurity: Breakthroughs in Treatment and Diagnosis

Posted by Ilena Di Toro | Posted on December 19, 2023

Having a child born prematurely poses numerous challenges for the parents. There is the additional time spent in the hospital, as well as concerns about the life and health of the baby. One concern is the potential development of retinopathy of prematurity, a form of blindness.

Retinopathy of prematurity happen when a premature baby comes from being inside the womb, which is a low oxygen environment to the incubator, which is a high oxygen environment. This leads to a sensation that the still-developing retina is receiving to much oxygen. That hinders normal blood vessel development. Interestingly enough, the retinal neurons keep growing in this situation. The end result is relative hypoxia or too little oxygen to the retina. This leads to more blood vessels in the retina, which leads to blindness.

Groundbreaking research done at the Medical College of Georgia at Augusta University and National Eye Institute (NEI) is studying ways of safeguarding premature babies’ vision and evaluating the necessity of treatment for this condition. Scientists at that the Medical College of Georgia found that a molecule, known as K604, can block the development of obstructive blood vessels, lessen inflammation and allow for more normal blood vessel growth. All of which leads to better vision for the babies.

The K604 molecule works by blocking ACAT1, an enzyme that converts free cholesterol and long-chain fatty acids to smaller cholesterol esters that can be easily eliminated by the liver to keep cholesterol level from getting too high. In premature babies experiencing retinal hypoxia, there is a build-up of lipids, fats and cholesterol esters, which exacerbates inflammation and triggers a cascade of events that promote abnormal blood vessel growth.

Since it was ACAT1’s role in allowing the cholesterol esters to build up in the retina, researchers wanted to see what would happen when they block the enzyme. Hypoxia increases the expression of the receptor that led to the movement of cholesterol into the retinal cells. This leads to the activation of ACAT1 and high levels of cholesterol ester. The esters promote inflammation, as well as the increased action of TREM1, a receptor in the myeloid cells that utilize short-term inflammation in response to being exposed to a virus.

Scientists saw the role TREM1 played in the development of blood vessels in the retina and they were able to demonstrate that TREM1 can prevent the blood vessels from forming in the retina in the first place. They also looked at inhibiting ACAT1, which is before TREM1 in the process and learned that it ACAT1 can do the same. It seems that the ACAT1 inhibition helps to restore normal metabolism in situation that is abnormal.

Since cholesterol levels increase during hypoxia, the microglial cells and macrophages, which are immune cells, make more ACAT1. Scientists suspect that the accumulation of the cholesterol esters make cells more inflammatory. As more microglial cells and macrophages come in, more cholesterol and lipids accumulate, ACAT1 expression increases, as well as the expression of vascular endothelial growth factor, or VEGF. The end results are inflammation and abnormal blood vessel growth. When cholesterol is removed from this situation, the damage stopped. The next step in this research would include a clinical trial of the K604 molecule in babies.

Of course, there needs to be a way to diagnose which premature babies have this condition in the first place. Usually, specialized equipment is used and trained technicians are needed to capture the images and evaluate the results. Not to mention, this type of camera can cost up to $150,000. Is there a cheaper and more simple way to get images of the eyes of premature babies?

Yes, and it something that many people already have—namely a smartphone.

Yes, you read correctly. Smartphones can be used to diagnose retinopathy of prematurity in premature babies. Research of a retinopathy of prematurity telemedicine program at Aravind Eye Hospital in India looked at 156 babies. The infants were screened for retinopathy of prematurity using a wide-field camera and one of two smartphone-based imaging devices, the Make-In-India Retcam or the Keeler Monocular Indirect Ophthalmoscope. The images were used to both determine if a baby had retinopathy of prematurity and if it required treatment. Researchers also trained an AI system to use the smartphone images to diagnose retinopathy of prematurity.

While the more specialized cameras can view a larger portion of the retina, clinicians and the AI program were able to identify babies with retinopathy of prematurity by way of images captured with a smartphone. The only area that the AI program had trouble with was in detecting mild retinopathy of prematurity. Still, researchers believe that smartphone-based images and an AI detection algorithm could help clinicians in low-resource setting to provide the proper treatment to babies with retinopathy of prematurity.

Innovative research at places like Medical College of Georgia at Augusta University and the utilization of smartphones to diagnose retinopathy of prematurity hold the potential to revolutionize care and support for premature babies facing vision-related challenges at birth. Of course, it would be nice if, once parents get the baby home, there weren’t so many midnight feedings.


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