Bilateral cytomegalovirus retinitis with vitreous hemorrhage leading to a false-positive (1,3)-β-D-glucan test after lung transplantation: a case report

Imagine your body is a high-tech fortress, and the immune system is the elite guard force patrolling the walls, keeping out unwanted invaders like bacteria and fungi. Usually, this guard force is very good at its job. But sometimes, to stop the fortress from attacking itself (like in autoimmune diseases) or to accept a brand-new organ transplant, doctors have to temporarily lower the guard's alert levels. This is called immunosuppression. While this saves the new organ, it leaves the gates a little more open than usual, giving microscopic troublemakers a chance to sneak in. One of these troublemakers is a virus called Cytomegalovirus (CMV), which loves to hide in the eyes of people with lowered defenses, causing a condition called retinitis that can blur vision or even cause blindness.

Now, imagine the doctors need a way to tell if a new invader is a fungus (which needs antifungal medicine) or just a glitch in the system. They use a special "sniffer test" called the (1,3)-β-D-glucan test. Think of this test like a metal detector at an airport. It's designed to beep loudly when it finds a specific type of metal (a fungal cell wall component) that shouldn't be there. If the detector beeps, the doctors usually assume there's a fungus and start treating for it. But what if the detector beeps not because of a metal, but because someone accidentally dropped a bag of confetti or a piece of red paint near the sensor? That's the tricky puzzle this paper explores: can something completely unrelated to fungi, like blood leaking into the eye, trick the detector into screaming "Fungus!" when there is none?

This paper tells the story of a 55-year-old man who had received a lung transplant a year earlier to treat a lung disease caused by breathing in dust (pneumoconiosis). Because his immune system was kept low to protect his new lung, he suddenly lost vision in his right eye. Doctors discovered he had CMV retinitis in both eyes, but the right eye had a nasty complication: a vitreous hemorrhage, which is basically a burst blood vessel causing blood to leak into the clear jelly inside the eye, and the retina was starting to peel away.

When the doctors took a sample of the fluid from the right eye to investigate, they found two things. First, the CMV virus was definitely there (confirmed by a positive CMV-DNA test). Second, the "metal detector" for fungi—the (1,3)-β-D-glucan test—went off with a very loud beep, showing a level of 293.43 pg/mL. This was confusing because the other tests for fungi (fungal culture and the galactomannan test) came back negative, saying "No fungus here."

Here is where the plot thickens. The left eye also had the virus, but it had no bleeding, and its (1,3)-β-glucan test was negative. The doctors treated the right eye with antiviral shots and surgery to remove the blood and fix the retina. Once the blood was cleared out, the (1,3)-β-D-glucan test in that eye went silent and turned negative. The story didn't end there, though. Later, the left eye suddenly started bleeding too, and guess what? The (1,3)-β-D-glucan test immediately became positive again. As soon as that bleeding was cleared, the test went negative once more.

The paper suggests that the blood leaking into the eye was the culprit, tricking the test into thinking there was a fungal infection when there wasn't one. It's as if the blood components acted like the confetti or red paint, causing a false alarm. The authors propose that this happens because the blood might activate the test in a non-specific way, change the environment inside the eye, or physically interfere with the sample. They note that these false alarms seem to happen more often when the test values are under 1000 pg/mL.

The main takeaway is a warning for doctors: if a lung transplant patient has CMV retinitis and eye bleeding, a positive fungal test might just be a "ghost" caused by the blood, not a real fungus. The paper argues that doctors shouldn't rush to give powerful antifungal drugs based on that single test. Instead, they should look at the whole picture—checking for actual fungus cultures, using other fungal tests, and watching how the numbers change over time. The real hero of the story is the early detection of the virus itself and the surgery to clear the blood, which saved the patient's vision and stopped the confusing false alarms.