Researchers from the Duke Eye Center in the United States may have solved a decades-old ophthalmic mystery – why people with Best disease often keep seeing clearly, despite a large, egg yolk-like deposit forming in the macula.
For people with Best vitelliform macular degeneration – or Best disease – the egg yolk-like deposit in the macula pushes the eye’s light-sensing photoreceptors away from the support cells that keep them alive. In theory, this separation should severely damage eyesight. Yet patients retain near-normal vision for years, even decades.
These protrusions are very fine and difficult to detect, even with powerful microscopes, which is why they had gone undetected until now
“This has been a persistent conundrum in ophthalmology,” said Professor Vadim Arshavsky. “Using electron microscopy and three-dimensional electron tomography, we were able to uncover how this is possible.”
Prof Arshavsky’s team found that when key retinal layers pull apart, the retinal pigment epithelium (RPE) sends out ultra-thin, thread-like extensions. These tiny bridges stretch across the widening gap, allowing the cells to keep doing the cleanup and renewal work needed to preserve vision.
The researchers discovered the structures while studying mice engineered to lack a gene called ADAM9. Best disease is caused by multiple gene mutations. The mice developed the same kind of enlarged space seen in human Best disease, yet their light-sensing cells kept functioning far longer than expected.
According to the study, published in the Journal of Clinical Investigation,2 this was due to the presence of the tiny extensions called pseudopods.
“These protrusions are very fine and difficult to detect, even with powerful microscopes, which is why they had gone undetected until now,” said Prof Arshavsky.
This discovery helps explain how vision can remain, even when the eye’s structure is disrupted. It could also inform new gene therapies now being tested for Best disease and similar conditions.
References
- Kirkendoll S, Duke University School of Medicine, Eye disease mystery solved: How Best disease patients keep seeing clearly, Duke University School of Medicine (online article) available at: medschool.duke.edu/news/eye-disease-mystery-solved-how-best-disease-patients-keep-seeing-clearly [accessed Feb 2026]
- Lewis TR, Castillo CM, Arshavsky VY, et al. Adam9-deficient retinal pigment epithelium pseudopods maintain photoreceptor outer segment renewal despite subretinal space expansion. J Clin Invest. 2026 Feb 5:e196705. doi: 10.1172/JCI196705. Epub ahead of print.
