Q&A: Kristina Pfau highlights rare genetic eye conditions

Christina Pfau, MD, FEBO, a consultant ophthalmologist from the University of Bonn, discussed her research on pseudoxanthoma elasticum (PXE), a rare genetic disease that shares similarities with age-related macular degeneration (AMD) at the 2025 EURETINA meeting. In the conversation, Pfau highlights her research using high-resolution OCT to examine PXE patients, revealing significant insights into retinal changes. She emphasizes the importance of multimodal imaging for accurate diagnosis, as PXE can mimic AMD and occur at various life stages.

The discussion explores the genetic basis of PXE, focusing on the ABCC6 gene and potential therapeutic approaches targeting pyrophosphate levels to prevent calcification. Pfau also stresses the systemic nature of the disease, recommending comprehensive medical care that extends beyond ophthalmology.

Note: The following conversation has been lightly edited for clarity.

Ophthalmology Times: What is the focus of your research?

Christina Pfau, MD, FEBO: My research focus is a disease called pseudoxanthoma elasticum, which is a rare disease, a genetic disease, and sometimes it has you have the same problems that you also have in age-related macular degeneration, [that's] why it's sometimes also confused. You have atrophy development, you have broadly rescuelization, with exudation, but more importantly, there are several therapeutic options coming up in the next years, so we really need a good outcome measure. Fortunately, we do have an high resolution OCT in Bonn. So, what we did was we examined really early stage PXE patients and looked at their high resolution OCT, and what we found was that their bruch membrane and RPE looks completely normal outside of the calcified area. Within the calcified area, we did see significant changes to the RPE bruch membrane complex. This is highly interesting, because if we can show over time that this changes, and we have a fantastic outcome measure for our future interventional trials.

OT: When does this disease begin to manifest for a patient?

Pfau: Pseudoxanthoma elasticum is a genetic disease, and genetic diseases normally occur early in life. So you can already think of something genetic if you have a patient having AMD phenotype, but it's a lot younger than always think of differential diagnosis like pseudoxanthoma elasticum and so on. But sometimes also pseudoxanthoma elasticum is occurring late onset, so it can also occur as a first manifestation in older age, and then it can really look like AMD. It looks like AMD, because they can get the neovascularization, atrophy, and you can treat them same as athe AMD patients, but you really have to do multimodal imaging to detect the disease. So really need a fluorescein angiography and a fungus autofluorescence to see the android streaks. They are radiating from the optic disc. Then also, if you look at the fundus, you can see the calcified area in pseudoxanthoma elasticum that is confined around the optic nerve, and outside you have normal, uncalcified Bruch membranes. So you have really a whitish area in the center and the red area in periphery. So if you look closely at your multimodal imaging, then it should be distinguishable. But beware that this can really look like AMD.

OT: What do we know about the geneic cause of this condition?

Pfau: That is super interesting, because the gene is just 1 gene, so it's ABCC6 and that encodes for a transporter in the liver. We don't know yet exactly what the transporter does, but what we know is that in the blood of these patients, pyrophosphate is decreased. All targeting options, now try to increase the level of pyrophosphate in the blood, so either by substituting it, or by inhibiting the degradation, so that you actually keep your own pyrophosphate longer active, and pyrophosphate, then, if it's high enough, actually inhibits calcification. So we really try to increase the pyrophosphate level in the blood of these patients.
Yes, if you have a patient with PXE, always think that it's a systemic disease, and you, as an ophthalmologist, can really make a difference. You have to send them to an angiologic center, because they get classification of arteries and the heart. So they really have to go-to check up and also be in the care of a general specialist and angiologist.